List of cocaine analogues

Cocaine with its numerical substitution position locants.
2′ (6′) = ortho, 3′ (5′) = meta & 4′ = para

This is a list of cocaine analogues. A cocaine analogue is a (usually) artificial construct of a novel chemical compound from (often the starting point of natural) cocaine's molecular structure, with the result product sufficiently similar to cocaine to display similarity in, but alteration to, its chemical function. Within the scope of analogous compounds created from the structure of cocaine, so named "cocaine analogues" retain 3β-benzoyloxy or similar functionality (the term specifically used usually distinguishes from phenyltropanes, but in the board sense generally, as a category, includes them) on a tropane skeleton, as compared to other stimulants of the kind. Many of the semi-synthetic cocaine analogues proper which have been made & studied have consisted of among the nine following classes of compounds:^{[lower-alpha 1]}

stereoisomers of cocaine
3β-phenyl ring substituted analogues
2β-substituted analogues
N-modified analogues of cocaine
3β-carbamoyl analogues
3β-alkyl-3-benzyl tropanes
6/7-substituted cocaines
6-alkyl-3-benzyl tropanes
piperidine homologues of cocaine

Alternate two-dimensional molecular diagram of cocaine; shown specifically as a protonated, NH+, hydrochloride, and disregarding 3D stereochemistry

However strict analogues of cocaine would also include such other potential combinations as phenacyltropanes & other carbon branched replacements not listed above. The term may also be loosely used to refer to drugs manufactured from cocaine or having their basis as a total synthesis of cocaine, but modified to alter their effect & QSAR. These include both intracellular sodium channel blocker anesthetics and stimulant dopamine reuptake inhibitor ligands (such as certain, namely tropane-bridged-excised, piperidines). Additionally, researchers have supported combinatorial approaches for taking the most promising analogues currently elucidated and mixing them to the end of discovering novel & efficacious compounds to optimize their utilization for differing distinct specified purposes.^{[lower-alpha 2]}

Two dimensional schematic drawing of cocaine's structural dynamic interaction points with dopamine transporter binding sites.

Although the carbmethoxy is denoted in its function as a hydrogen bond in this depiction, it has been found that it is primarily eletrostatic factors which dominate binding within this space of the molecular surface area over the operative principle of hydrogen bonding.^{[lower-alpha 3]}

Two out of three potential "reverse esters" of cocaine (the third one being a single "di-substituted" structure with both the 'methyl ester' & 'benzoate' reversed in tandem)

Analogs sensu stricto

Cocaine Stereoisomers

There are eight stereoisomers of cocaine (with the internal portion of the tropane ring unchanged).^{[lower-alpha 4]} Not counting mesomers but including the one & five to eight position bond bridge of the tropane system having R- & S- configurations potentially, cocaine can be counted as having as many as sixteen stereoisomers.

Stereoisomer	S. Singh's alphanumeric assignation	IC₅₀ (nM) [³H]WIN 3542 inhibition to rat striatal membranes Mean error standard ≤5% in all cases	IUPAC nomenclature
R-cocaine	—	102	methyl(1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
R-pseudococaine	172	15800
R-allococaine	173	6160
R-allopseudococaine	174	28500
S-cocaine	175	15800
S-pseudococaine	176	22500
S-allococaine	177	9820	methyl(1S,3S,4R,5R)-3-(benzoyl)oxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate
S-allopseudococaine	178	67700

Where the 2D diagrams given for the structural analogs below do not indicate stereochemistry, it should be assumed they share the conformation of R-cocaine, unless noted otherwise.

The natural isomerism of cocaine is unstable in several ways besides having a high degree of lability; for instance: the C2 carbmethoxy in its biosynthesis end-product maintains the axial position, which can undergo epimerization via saponification to obtain the former in an equatorial position.

The creation of the following analogues of cocaine have traditionally required a step which has utilized 2-CMT as an intermediate molecular product.

Benzoyl branch cleavage substitutions (excluding the exhaustive phenyl group)

Salicylmethylecgonine^[2]	Methylvanillylecgonine^[3]^[4]

N.B. Fries rearrangement product of aspirin used to make salbutamol. It is relevant to the precursor here though because the migrated acetyl group can be the subject of a haloform reaction. A more direct route to vanillic acid though is just oxidation of the vanillin to a functionalized benzoic acid.

Arene benzene-ring 2′, 3′, 4′ (5′ & 6′) position (aryl) substitutions

para-substituted benzoylmethylecgonines

Carbon 4′-hydrogen Substitutions (benzene-4′ "*para*" substituted benzoyloxytropanes)^{[lower-alpha 5]}
^{Data-set congruent to, and aggregate with, following tables
IC₅₀ values}
Structure	S. Singh's alphanumeric assignation (name)	4′=R	DAT [³H]WIN 35428	5-HTT [³H]Paroxetine	NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT
	(cocaine)	H	249 ± 37	615 ± 120	2500 ± 70	2.5	10.0
non-benzoyloxy analogue comparative ligands _{non-tropane analogue comparative ligands}	11b (WIN 35428) _(nisoxetine) ^(fluoxetine)	F _— ^—	24 ± 4 _{775 ± 20} ^{5200 ± 1270}	690 ± 14 _{762 ± 90} ^{15 ± 3}	258 ± 40 _{135 ± 21} ^{963 ± 158}	28.7 _1.0 ^0.003	10.7 _0.2 ^0.2

	183a	I	2522 ± 4	1052 ± 23	18458 ± 1073	0.4	7.3
	183b	Ph	486 ± 63	-	-	-	-
	183c	OAc	144 ± 2	-	-	-	-
	183d	OH	158 ± 8	3104 ± 148	601 ± 11	19.6	3.8
	(4′-Fluorococaine)^[5]	F	-	-	-	-	-
	(para-Isothiocyanatobenzoylecgonine methyl ester)^[6] (p-Isococ)	NCS	-	-	-	-	-

The MAT binding pocket analogous to the lipophilic place on cocaine-like compounds, inclusive of the benzene ring, is approximate to 9 Å in length. Which is only slightly larger than a phenyl ring by itself.^{[lower-alpha 6]}

meta-substituted benzoylmethylecgonines

Carbon 3′-hydrogen Substitutions (benzene-3′ "*meta*" substituted benzoyloxytropanes)^{[lower-alpha 7]}
^{Data-set congruent to, and aggregate with, preceding and following tables
IC₅₀ values}
S. Singh's alphanumeric assignation (name)	3′=R	DAT [³H]WIN 35428	5-HTT [³H]Paroxetine	NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT

184a	I	325^ɑ	-	-	-	-
184b	OH	1183 ± 115	793 ± 33	3760 ± 589	0.7	3.2
191	OBn	-	-	-	-	-
(m-Isococ)	NCS	-	-	-	-	-

^ɑIC₅₀ value for displacement of [³H]cocaine

ortho-substituted benzoylmethylecgonines

The hydroxylated 2′-OH analogue exhibited a tenfold increase in potency over cocaine.^{[lower-alpha 8]}

Carbon 2′-hydrogen Substitutions (benzene-2′ "*ortho*" substituted benzoyloxytropanes)^{[lower-alpha 9]}
^{Data-set congruent to, and aggregate with, preceding and following tables
IC₅₀ values}
S. Singh's alphanumeric assignation (name)	2′=R	DAT [³H]WIN 35428	5-HTT [³H]Paroxetine	NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT

185a	I	350^ɑ	-	-	-	-
185b	F	604 ± 67	1770 ± 309	1392 ± 173	2.9	2.3
185c (2′-Acetoxycocaine)^[7]	OAc	70 ± 1	219 ± 20	72 ± 9	3.1	1.0
185d (2′-Hydroxycocaine)^[2]	OH	25 ± 4	143 ± 21	48 ± 2	5.7	1.9

^ɑIC₅₀ value for displacement of [³H]cocaine

manifold benzoyloxy phenyl-substitutions

Multi-substitutions (substitutions of substitutions; e.g. meta- & para-) or manifold ("many-fold") substituted analogues are analogues where more than one modification from the parent molecule takes place (having numerous intermediary constituents). These are created with often surprising structure–activity relationship results extrapolated therefrom. It is even a common case where two separate substitutions can each yield a weaker, lower affinity or even wholly non-efficacious compound respectively; but due to findings that oftentimes, when used together, such two mutually inferior changes being added in tandem to one analogue has the potential to make the resultant derivative display much greater efficacy, affinity, selectivity &/or strength than even the parent compound; which otherwise was compromised by either of those two alternations when made alone.

For an exposition & allusion to this mechanism observe that the opioid oxycodone, derived from codeine, is 1.5×—1.7× the analgesic potency of morphine (an opioid to which codeine is by comparison only 8%—12% as potent relatively, or 0.17th its strength in rats); yet oxycodone's intermediates in its synthesis from codeine are: ⅓ the potency of codeine (i.e. codeinone); 0.13 that of morphine (i.e. 14-hydroxycodeine) in rats and less in mice (to illustrate: the former even being less than the 0.17 of morphine that codeine is); with the final possible stand alone intermediate compound between codeine & oxycodone (i.e. 7,8-dihydrocodeine) being at most 150% to 200% that of codeine.^[8]

Manifold Compositions of Terminating Phenyl Ring Substitutions (Multiple benzene-2′,3′ & 4′ combined substituted benzoyloxytropanes)^{[lower-alpha 10]}
^{Data-set (excepting instanced references inside table) congruent to, and aggregate with, preceding and following tables
IC₅₀ values}
Structure	S. Singh's alphanumeric assignation (name)	ortho-2′=R	meta-3′=R	para-4′=R	DAT [³H]WIN 35428	5-HTT [³H]Paroxetine	NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT
	186	HO	H	I	215 ± 19	195 ± 10	1021 ± 75	0.9	4.7
	(Vanillylmethylecgonine)^[3]	H	OCH₃	OH	-	-	-	-	-

benzoyl phenyl-alterations

The naphthalene analogs allow for further numeric substitutions, including eight position peri substituted patterns. Many more alterations creating differing aromatic rings are possible.

Terminating Phenyl Carbon Ring Fusions & Alterations^{[lower-alpha 11]}
^{Data-set congruent to, and aggregate with, preceding table
IC₅₀ values}
Structure	S. Singh's alphanumeric assignation (name)	C=R	DAT [³H]Cocaine (IC₅₀)	5-HTT [³H]Paroxetine	NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT
	187	1-naphthalene	742 ± 48	-	-	-	-
	188	2-naphthalene	327 ± 63	-	-	-	-

Benzoyl branch modifications

Parent compound of a series of spirocyclic cocaine benzoyl linkage modification analogs created by Suzuki coupling method of ortho-substituted arylboronic acids and an enol-triflate derived from cocaine.^[9]

Benzoylthiomethylecgonine^[10]

A sulfur in place of the oxygen at the benzoyl ester single bond results in a lower electronegativity than that of cocaine.

2β-substitutions (including transesterification metabolite substitution cocaethylene)

The consideration that large, bulky C2 substituents would alter the tropane by distorting the piperidine ring part of its skeleton sufficiently enough to impair its functionality, or that in said event such would hamper binding, in particular at the 8-aza end to ease steric strain going toward its place from the 2-position,^{[lower-alpha 12]} appear to in many cases be unfounded.^{[lower-alpha 13]} (examples shown in collapsed/bundled table of images below)

Intermediate compound #203

Additional 2β-Cocaine analogue molecular structures

Compounds with greater SERT affinity than cocaine parent (slightly less @ DAT, significantly less, except for #196g, @ NET)

Compounds with greater DAT affinity than cocaine parent (SERT & NET affinity untested; note however their similarity to more potent SERT ligands above)			(greater)>@ DAT, (lesser)<@ SERT, (much less)<<@ NET

Compound 197b displayed a 1,131-fold increased selectivity in affinity over the serotonin transporter, with only slight reductions in potency for the dopamine & norepinephrine transporters.^{[lower-alpha 14]} Whereas 197c had a 469× increase at SERT, with greater affinity for DAT than cocaine & was approximately equipotent to NET.^{[lower-alpha 15]} 197b was 137×, and 196c 27× less potent at binding to the serotonin transporter, but both had a NET / DAT ratio that made for a better dopaminergic than cocaine.^{[lower-alpha 16]}

Direct 2β Substitutions^{[lower-alpha 17]}
^{(IC₅₀ nM values)}
S. Singh's alphanumeric assignation (name)	R	DAT [³H]WIN 35428	5-HTT [³H]Paroxetine	NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT

(Cocaine)	Me	89 ± 4.8	1045 ± 89	3298 ± 293	11.7	37.0
196a (Cocaethylene)	Et	195 ± 45	5801 ± 493	10000 ± 751	29.7	51.3
196b	n-Pr	196 ± 46	4517 ± 430	6124 ± 262	23.3	31.2
196c	i-Pr	219 ± 48	25224 ± 1498	30384 ± 1685	115	139
196d	Ph	112 ± 31	33666 ± 3330	31024 ± 1909	300	277
196e	Bn	257 ± 14	302 ± 23	20794 ± 950	1.2	80.9
196f	β-phenethyl	181 ± 10	615 ± 52	19944 ± 1026	3.4	110
196g	γ-phenylpropyl	147 ± 19	374 ± 15	4893 ± 344	2.5	33.3
196h	cinnamyl	371 ± 15	368 ± 6.3	68931 ± 3476	1.0	186
196i	p-NO₂-β-phenethyl	601 ± 28	-	-	-	-
196j	p-Cl-β-phenethyl	271 ± 12	-	-	-	-
196k	p-NH₂-β-phenethyl	72 ± 7	-	-	-	-
196l	p-NCS-β-phenethyl	196 ± 14	-	-	-	-
196m	p-azido-β-phenethyl	227 ± 19	-	-	-	-
196n	(p-NHCOCH₂Br)β-phenethyl	61 ± 6	-	-	-	-
196o	(p-NHCO(CH₂)₂CO₂Et)β-phenethyl	86 ± 4	-	-	-	-
197a	NH₂	753 ± 41.3	13725 ± 1256	3981 ± 229	18.2	5.3
197b	-NMe₂	127 ± 6.36	143713 ± 8854	7329 ± 158	1131	57.7
197c	-N(OMe)Me	60 ± 6.4	28162 ± 2565	3935 ± 266	469	65.6
197d	-NHMe	2424 ± 118	44798 ± 2105	4213 ± 206	18.5	1.7
197e (Benzoylecgonine)	-OH	195000	-	-	-	-
197f	HOCH₂-	561 ± 149	-	-	-	-
197g (Tropacocaine)	H	5180 ± 1160	-	-	-	-

Bioisostere 2-position carbmethoxy-ester functional replacements

Benzoylecgonine, i.e. compound 197e, (differing from its cocaine parent only by de-methylation of the C2 carbmethoxy to that of a carboxy) has an extreme loss in potency (its approximate affinity being 195,000 nM) as displayed by in vitro methodologies for determining binding efficacy (wherein BBB penetration does not factor-in on the matter in the manner as in vivo studies) and is posited to be due possibly to zwitterion formation.^{[lower-alpha 18]}

2β-isoxazole and isoxazoline ring containing analogues^{[lower-alpha 19]}
^{Data-set congruent to, and aggregate with, following tables
IC₅₀ nM values}
S. Singh's alphanumeric assignation (name)	R	[³H]Mazindol	[³H]DA	Selectivity Uptake/Binding
(Cocaine)	(H)	580 ± 70	570 ± 180	1.0

198a	H	520 ± 40	260 ± 70	0.5
198b	CO₂Et (5′-carboethoxy-)	120 ± 10	290 ± 40	2.4
198c	BOC	2230 ± 220	1820 ± 810	0.8
198d	Ph	2000 ± 640	2920 ± 1620	1.5
198e	CH=CHCO₂Me	3600 ± 400	3590 ± 1180	1.0

[²H₃-N-methyl]-cocaine: reagent analogue used in radio-labeling ligand binding sites.

nonplanar 2β-isoxazoline ring containing analogues^{[lower-alpha 20]}
^{Data-set congruent to, and aggregate with, preceding and following tables
IC₅₀ nM values}
S. Singh's alphanumeric assignation	R	[³H]Mazindol	[³H]DA	Selectivity Uptake/Binding

199a	β(or R)CO₂Et	710 ± 150	1060 ± 340	1.5
199b	α(or S)CO₂Et	5830 ± 630	8460 ± 620	1.4

2β-isoxazoline atomically N/O reversed analogues^{[lower-alpha 21]}
^{Data-set congruent to, and aggregate with, preceding and following tables
IC₅₀ nM values}
Structure	S. Singh's alphanumeric assignation	R	[³H]Mazindol	[³H]DA	Selectivity Uptake/Binding
	200		880 ± 350	400 ± 140	0.4

Vinylogous 2β-position carbmethoxy-ester functional replacements

201b & 201c show significant increased potency over cocaine; whereas 201a, 201d & 201e are considerably less so. This infers the hydrogen bond acceptor at the 2β position to not necessarily be of exclusive import in creation of higher binding analogues of cocaine.

[²H₅-phenyl]-cocaine: reagent analogue, as above thumbnail of similar compound: rendered from its cocaine parent by replacing a cluster of several adjacent hydrogens (from among the hydrogens that comprise the entire circumference common to every basic molecular perimeter) with deuterium, in an equivalent but localized spread or cluster.

vinylogous 2β analogues^{[lower-alpha 22]}
^{Data-set congruent to, and aggregate with, preceding table
IC₅₀ nM values}
S. Singh's alphanumeric assignation	R	[³H]Mazindol	[³H]DA	Selectivity Uptake/Binding

201a	H	1730 ± 550	1120 ± 390	0.6
201b	Cl	222 ± 49	368 ± 190	1.6
201c	CO₂Et	50 ± 10	130 ± 10	2.6
201d	CH=CHCO₂Et	1220 ± 100	870 ± 50	0.7
201e	PO(OEt)₂	4850 ± 470	5500 ± 70	1.1

N-modifications

Additional N-modified cocaine analogue molecular structures

8-oxa cocaine analogs:^[11] (cf Meltzer with PTs)

Nitrogen Substitutions
Mazindol comparison table
(^ɑβ-CFT comparison notation)^{[lower-alpha 23]}
S. Singh's alphanumeric assignation (name)	N8-R	[³H]Mazindol binding	[³H]DA uptake	Selectivity Uptake/Binding
217 (Cocaine methiodide)	-	10700 ± 1530^ɑ	-	-
(Cocaine)	CH₃	280 ± 60 102^ɑ	320 ± 10	1.1
218 (Norcocaine)	H	303 ± 59^ɑ	-	-
219a	Bn	668 ± 67^ɑ	-	-
219b	Ac	3370 ± 1080^ɑ	-	-
219c	CH₂CH₂OH	700 ± 100	1600 ± 200	2.3
219d	CH₂CO₂CH₃	480 ± 40	1600 ± 100	3.3
219e	CH₂CO₂H	380 ± 20	2100 ± 400	5.5
220a	SO₂CH₃ (Ms)	1290 ± 80	1970 ± 70	1.5
220b	SO₂CF₃ (Tf)	330 ± 30	760 ± 20	2.3
220c	SO₂NCO	120 ± 10	160 ± 10	1.3
220d	SO₂Ph	20800 ± 3500	61000	2.9
220e	SO₂C₆H₄-4-NO₂ (nosyl)	5720 ± 1140	18800 ± 90	3.3
220f	SO₂C₆H₄-4-OCH₃	6820 ± 580	16400 ± 1400	2.4
221a	NO	99500 ± 12300	231700 ± 39500	2.3
221b	NO₂	7500 ± 900	21200 ± 600	2.8
221c	NHCOCH₃	>1000000	>1000000	-
221d	NH₂	-	-	-

^ɑIC₅₀ (nM) for displacement of [³H]WIN 35428

Tropane fused/bridged (N-constrained/tethered) analogues

A selection of "front bridged" & "back bridged" cocaine analogs.

Derivations upon fusions of the tropane's nitrogen bridge^{[lower-alpha 24]}
Compound	S. Singh's alphanumeric assignation	R	[³H]Mazindol	[³H]DA	Selectivity Uptake/Binding
	222		44900 ± 6200	115000 ± 15700	2.6

Back-bridged cocaine analogues are considered more akin to untethered cocaine analogs & phenyltropane derivatives (where the nitrogen lone pair is not fixed or constrained) and better mimics their affinities. This is due to when the eighth carbon tropane position is freely rotatable and unbound it preferably occupies the axial position as defining its least energy & most unhindered state. In front-bridged analogs the nitrogen lone pairings rigid fixity makes it reside in an equatorial placing for the piperidine ring-part of the tropane nucleus, pointing to the two-carbon & three methylene unit bridgehead; giving the attested front-bridged cocaine analogues preference for SERT over DAT.^{[lower-alpha 25]}

Constrained thiophene tropane^[12]^[13] Note the pi symmetry of the partially hydrogen-unsaturated cyclopentane substitutes the benzene place with the other tricyclic tropanes to the right.

Tricyclic tropanes, values in K_i (nM)^[14]
1st structure (di-chloro benzene, 2β-CH₂OCOMe) SERT = 1.6, DAT = 1870, NET = 638
2nd structure (para-bromo, meta-chloro, 2β-CO₂Me) SERT = 2.3, DAT = 5420, NET = 459
3rd structure (para-iodo, meta-chloro, 2β-CH₂OCOPh) SERT = 0.06, DAT/NET both = >10K

6/7 tropane position methoxycocaine & methoxypseudococaine analogues

Substitutions upon the 6 & 7 positions of the tropane^{[lower-alpha 26]}
S. Singh's alphanumeric assignation (name)	X	K_i (nM) [³H]Mazindol binding	K_i (nM) [³H]DA uptake	Selectivity Uptake/Binding
(Cocaine)		280 ± 60	320 ± 10	1.1
(Pseudococaine)		10400 ± 300	13800 ± 1500	1.3

225a	2β, 6β-OCH₃	98000 ± 12000	68000 ± 5000	0.7
225b	2α, 6β-OCH₃	190000 ± 11000	510000 ± 110000	2.7
225c	2β, 7β-OCH₃	4200 ± 100	6100 ± 200	1.4
225d	2α, 7β-OCH₃	45000 ± 5000	110000 ± 4000	2.4
225e	2α, 7α-OCH₃	54000 ± 3000	200000 ± 70000	3.7

Carbon position 2′—(6′) & 2β-substitution combination analogues

4′-Iodococaine-2β-substituted analogues^{[lower-alpha 27]}
S. Singh's alphanumeric assignation	2β-R	C2′-R	IC₅₀ (nM) (displacement of [³H]WIN 35428)

211a	CO₂OH	H	6214 ± 1269
211b	CH₂OCOCH₃	H	2995 ± 223
211c	CONHCH₃	H	>100000
211d	CO₂Et	H	2031 ± 190
211e	CO₂-i-Pr	H	1377 ± 10
211f	CO₂Ph	H	2019 ± 253
211g	CO₂CH₂Ph	H	4602 ± 325
211h	3-phenyl-1,2,4-oxadiazole	H	3459 ± 60

211i	CH=CH₂	H	2165 ± 253
211j	CH₂CH₃	H	2692 ± 486
212	CH₂CH₃	HO	663 ± 70 4507 ± 13^ɑ 34838 ± 796^b

^ɑFor displacement of [³H]paroxetine (5-HTT & NET)
^bFor displacement of [³H]nisoxetine (5-HTT & NET)

3β-Carbamoyl analogues

3-position carbamoyl linkage substituting benzoyloxy analogues^{[lower-alpha 28]}
S. Singh's alphanumeric assignation (name)	X	IC₅₀ (nM) inhibition of [³H]Cocaine binding (Rat Striatal Tissue)	IC₅₀ (nM) inhibition of [³H]DA uptake (Rat Striatal Tissue)	Selectivity uptake/binding
(Cocaine)	(H)	70 ± 10	210 ± 70	3.0

223a	H	5600 ± 700	52600 ± 3000	9.4
223b	4-NO₂	1090 ± 250	5700 ± 1200	5.2
223c	4-NH₂	63300 ± 12200	>100000	-
223d	4-N₃	1000 ± 240	1180 ± 360	1.2
223e	4-NCS	260 ± 60	490 ± 80	1.9

223f	3-NO₂	37 ± 10	178 ± 23	4.8
223g	3-NH₂	2070 ± 340	23100 ± 900	11.1
223h	3-N₃	630 ± 150	3900 ± 1590	6.2
223i	3-NCS	960 ± 210	4900 ± 420	5.1

Phenyl 3-position linkage substitutions

A 3-Dimensional (stick-&-ball) rendering of Troparil: A structural analogue of cocaine with omitted -COO- linkage – a parent compound of many MAT ligands; those of the phenyltropane class. (Here it is depicted in an unfavourable conformation of the O-Me; The methyl has to be at the other oxygen and trans to optimize its functional stimulation.)

The top image above is a 2-Dimensional emulation of the orientation for the animated 3D image to the far right, with a methoxy that is distal from the phenyl group and cis. While the alternate image below that to its bottom shown above is one with the carboxyl methyl group proximal to the phenyl, in its optimum conformation, with a likewise optimum trans configuration.

See: List of phenyltropanes (Many phenyltropanes are derived from cocaine metabolites, such as methylecgonidine, as precursors)

The difference in the length of the benzoyloxy and the phenyl linkage contrasted between cocaine and phenyltropanes makes for a shorter distance between the centroid of the aromatic benzene and the bridge nitrogen of the tropane in the latter PTs. This distance being on a scale of 5.6 Å for phenyltropanes and 7.7 Å for cocaine or analogs with the benzoyloxy intact.^{[lower-alpha 29]} This may account for PTs increased behavioral stimulation profile over cocaine.^{[lower-alpha 30]} Differences in binding potency have also been explained considering solvation effects; cocaine containing 2β,3β-ester groups being calculated as more solvated than the WIN-type compounds (i.e. troparil). Higher pK_ɑs of the tropane nitrogen (8.65 for cocaine, 9.55 for troparil & 11.95 for vinyl analogue 43a), decreased aqueous solvation & decreased conformational flexibility added to increased binding affinity.^{[lower-alpha 31]}

Despite the observation of increased stimulation, phenyltropanes lack the local anesthetic sodium channel blocking effect that the benzoyloxy imparts to cocaine. Beside topical affect, this gives cocaine an affinity for binding to sites on the dopamine and serotonin sodium dependent transport areas that are distinct & specific to MAT in contrast to the general sodium channels; creating a separate mechanism of relational affinity to the transporters in addition to its inhibition of the reuptake for those transporters; this is unique to the local anesthetic value in cocaine & analogues with a similar substitute for the benzoyloxy that leaves the sodium channel blockage ability intact. Rendering such compounds as different functionally in their relation to MAT contrasted to phenyltropane analogues which have the local anesthetic bridge removed.^[15] In addition, it even has been postulated that a crucial role regarding the electron energy imparted via voltage sensitization (and thus action potential blockage with a molecule capable of intersecting its specific channel, in the case of cocaine a sodium channel, then acting upon atomic scale triboelectric effect that potentially serves in re-quantifying its charge) upon a receptor binding site may attenuate the mediating influence of the inhibitory regulation that autoreceptors play by their slowing neurotransmitter release when an efflux is created through an instance of agonism by a compound; allowing said efflux to be continued without the body's attempt to maintain homeostasis enacting in as readily responsive a manner to its conformational change.^[16]

Various phenyltropane examples

3β-Alkylphenyltropane & 3β-Alkenyl analogues

The compound 224e, the 3β-styrene analogue, had the highest potency in its group. While 224b & 224c showed the most selectivity, with 224b having a ten-fold greater potency for the dopamine transporter than cocaine.^{[lower-alpha 32]}

3β-styrene alkylphenyl cocaine analog image showing stereochemistry.
(i.e. compound "224e")

3-position alkylphenyl linkage substituting benzoyloxy analogues^{[lower-alpha 33]}
S. Singh's alphanumeric assignation (name)	n	IC₅₀ (nM) [³H]Cocaine binding	IC₅₀ (nM) [³H]DA uptake	Selectivity uptake/binding
(Cocaine)		101 ± 26	209 ± 20	2.1

224a	₁	885 ± 18	1020 ± 52	1.1
224b	₂	9.9 ± 0.33	70.5 ± 1.0	7.1
224c	₃	344 ± 12	2680 ± 190	7.8
224d		71.6 ± 0.7	138 ± 9	1.9
224e		2.10 ± 0.04	5.88 ± 0.09	2.8

6-Alkyl-3-benzyltropane analogues

Cocaine 229b—f series analogues

Cocaine 230b—f series analogues

Cocaine 231c—f series analogues

Cocaine 232c, d & f series analogues

6-Alkyl-3-benzyl-2[(methoxycarbonyl)methyl]tropane analogues^{[lower-alpha 34]}
S. Singh's alphanumeric assignation (name/WIN number)	R	K_i (nM) [³H]WIN 35428 binding	IC₅₀ (nM) [³H]DA uptake	Selectivity uptake/binding
(Cocaine)		32 ± 5 338 ± 221	405 ± 91 405 ± 91	12.6 1.2
11a (WIN 35065-2)		33 ± 17 314 ± 222	373 ± 10	11.3

(−)-229a	H	33 ± 5	161 ± 100	4.9
229a	H	91 ± 10	94 ± 26	1.0
229b	Me	211 ± 23	-	-
229c	Et	307 ± 28	-	-
229d	n-Pr	4180 ± 418	-	-
229e	n-Bu	8580 ± 249	-	-
229f	Bn	3080 ± 277	-	-

(+)-230a	H	60 ± 6	208 ± 63	3.5
230a	H	108 ± 14	457 ± 104	4.2
230b	Me	561 ± 64	-	-
230c	Et	1150 ± 135	-	-
230d	n-Pr	7240 ± 376	-	-
230e	n-Bu	19700 ± 350	-	-
230f	Bn	7590 ± 53	-	-

231b	Me	57 ± 5	107 ± 36	1.9
231c	Et	3110 ± 187	-	-
231d	n-Pr	5850 ± 702	-	-
231f	Bn	1560 ± 63	-	-

232b	Me	294 ± 29	532 ± 136	1.8
232c	Et	6210 ± 435	-	-
232d	n-Pr	57300 ± 3440	-	-
232f	Bn	3080 ± 277	-	-
241	Bn	4830 ± 434	-	-

Benzylidene derivatives of 6-alkyl-3-benzyltropanes^{[lower-alpha 35]}
Sub-category (S. Singh compound #)	a R=H	b R=Me	c R=Et	d R=n-Pr	e R=n-Bu	f R=Bn
6α-isomers: 237a—f
6α-isomers: 237a—f
6β-isomers (exo): 238a—f
6β-isomers (exo): 238a—f
3β-benzyl derivatives: 239a—f
3β-benzyl derivatives: 239a—f
intermediate alkylidene esters: 240a—f
intermediate alkylidene esters: 240a—f

N.B. that 237a and 238a are the same compound as both are the parent for either series with a hydrogen saturated in their respective substitution place.

Piperidine cocaine-homologues

binding potency of piperidine homologues for displacement of [³H]WIN 35428^{[lower-alpha 36]}
S. Singh's alphanumeric assignation (name)	2β-R	IC₅₀ (nM)
(Cocaine)	CO₂CH₃ (i.e. CO₂Me)	249 ± 37
183a	CO₂CH₃	2522 ± 4

242	H	11589 ± 4
243	CO₂CH₃	8064 ± 4

Cocaine hapten analogues

"GNC", a cocaine analog designed to minimize the formation of noncocaine-like structures through its chemical coupling to the Ad proteins; all while maintaining the element of its antigenic determinant from the moiety of cocaine.^[17]

Cocaine analogs which elicit noncatalytic antibodies^{[lower-alpha 37]}
Compound	S. Singh's alphanumeric assignation (name)	2β-R
	394 (GNC)	CO₂(CH₂)₅CO₂H
	395	CO₂CH₃
	396	CONH(CH₂)₅CO₂H

Tetrahedral-intermediate cocaine-hapten compound #400

Cocaine transition state analogues (TSAs) which generate catalytic antibodies^{[lower-alpha 38]}
Compound	S. Singh's alphanumeric assignation (name)	R

	401a	CH₃
	401b	(CH₂)₅CO₂H
	401c	CH₂CO₂H
	401d	COCH₂CH₂CO₂H
	401e	H
	401f	CH₂CH₂Br
	385g	(CH₂)₂NHCO(CH₂)₂CONH₂

	402a	O(CH₂)₄NHCO(CH₂)₂CO₂…2,3-dihydro-1H-isoindole-1,3-dione
	402b	OH
	402c	O(CH₂)₂…1,4-xylene…NH₂
	402d	NH(CH₂)₅CO₂H
	402e	O(CH₂)₄NHCO(CH₂)₂CONH₂

	403a	NH₂
	403b	NHCOCH₂Br
	403c	NHCO(CH₂)₃CO₂H
	403d	(CH₂)₃NHCO(CH₂)₂CONH₂

Anti-idiotypic & butyl-cholinesterase mediated immunopharmacotherapy cocaine analogs^[18]
Compound	Name

	K1-KLH/BSA^[19]

	K2-KLH/BSA

Structural/Functional intermediate analogues

Tropane (non-ecgonine) analogues

The first compound of those categorized as an "intermediate analog" in the series presented immediately below (para-fluoro-benzoyl-tropane), although several modifications distant from its cocaine parent structure, fits every technical criteria of a strict analog type to cocaine. It is given here, however, as the nearest relational structure along the instanced spectrum trajectory of substituent permutations of those following from it (in this first section), and set it as the beginning ingress point for the range of those comparable but sufficiently divergent from those in full homogeneity of structure and function to distinguish a more median class that is not in as much a rigid stereotyped placement to both (and not yet approaching the fringe or outermost terms allowing inclusion)

Tematropium, an anticholinergic that diverges from the MAT relational criteria for being a functional analog to cocaine.^[20] (cf. tropatepine)

pFBT: Zatosetron: Tropanserin: Bemesetronum:

3-(p-Fluorobenzoyloxy)tropane (30% stimulant potency of cocaine & equipotent as an anaesthetic)
Zatosetron (anxiolytic & antinauseant 5HT₃ receptor antagonist)
Tropanserin (migraine medication, potent & selective 5HT₃ antagonist)
Bemesetronum (antiemetic, mechanisms related to oxytocin function, serotonin D-receptors, cholinoreceptors of the muscarinic or nicotinic kind and histamine H₁-receptors^[21])

cf. Tropisetron

Convolamine: Phyllalbine:
Similarly, many natural tropane alkaloids found in plants of various families have benzoyl tropane structures. Including; catuabine, convolamine of the convolvulaceae & phyllalbine of euphorbiaceae (Phyllanthus discoïdes) families. The latter is a central and peripheral sympathomimetic drug.^[22] Phyllalbine is also to methylvanillylecgonine what tropacocaine, as a metabolite, is to cocaine. Likewise vanillin would be a hydrolytic degradation product of phyllalbine just as methyl benzoate is for cocaine.

Other tropanyl compounds (naturally found or otherwise) begin to fall outside the spectrum of functional analogues to cocaine altogether; having negligible affinity of any kind for the monoamine system. Compare for example ipratropium, mirisetron, technepine, levomepate or scopolamine & atropine. Many of the natural varieties being deliriants.

NK-1145: EGIS-3886: cpd #278^{[lower-alpha 39]} (mono-phenyl benztropine):
The benzoyloxy can even be replaced with other branch formations (terminating in a benzene ring) and the bridge between will still serve to create a parasympatholytic drug compound that causes behavioral stimulation, as the above: NK-1145 "tropine-3β-phenyl ether."^[23] Deramciclane (EGIS-3886) is a camphor derived serotonergic. Similar to several other kinds of aromatics in structure and being an inverse agonist at the 5-HT_2C receptor as well as an antagonist at the 5-HT_2A.

Azaprocin: Pseudotropinearylether:

Azaprocin (a fast onset, short duration opioid analgesic with tropane emulating every constituent element shared by cocaine; somewhat similar to how fentanyl overlays methylphenidate, save for in that case there's an additional constituent of a phenylethyl tail). Also of note: the arene-fluorinated pseudotropinearylether with respect to U.S. Patent 4,861,889

Piperidine Analogues

3-dimensional (space-filling) rendering of piperidine structure-based, MAT re-uptake inhibiting functional stimulant: "methylphenidate" (MPH)

See: List of methylphenidate analogues

Many of the piperidine analogues of cocaine serve as the 'missing link' between the cocaine structure and that of the methylphenidate class of drugs. For example, DMNPC preserves an orientation similar to the phenyltropanes, but is a structural isomer of methylnaphthidate.

The above depicts the 3D structure of the above-mentioned methylnaphthidate shown with the same modeling for the cocaine derivative WIN 35428, a simple phenyltropane with a short addition to its para position. This overlay shows the closeness of where the two hold their respective oxygen and nitrogens in their structure (also their benzene & cycloalkane ring formations) and is meant to convey a sense of their similarity for binding to MAT. Correspondingly most other monoamine reuptake inhibitors bind to the dopamine transporter substrate recognition site at Tm loci 1, 7 & 10—12; whereas cocaine & methylphenidate similarly share the 1 & 7 places, but diverge from the usual ligand site of the latter and instead cohabit the 9—11 loci.^{[lower-alpha 40]} Site-directed mutagenesis techniques have elucidated that the hydrophobic putative transmembrane regions at one & seven contain aspartate and serine residues, and that the carboxyl-group interacts with the former aspartic acid residue 79 which engages with cocaine & methylphenidate's protonated nitrogen at the transporter.^{[lower-alpha 41]} Previous theories of an allosteric site for cocaine and related compounds which do not overlap with the binding site of dopamine itself are less prevalent in light of more recent observations since LeuT became feasible as a modeling template.^[25]

One rationale to denote the subjective preference for cocaine over methylphenidate in animal habituation & human addiction models has to do with the respective difference in their entropy of binding: cocaine being —5.6 kcal/mol & methylphenidate being —25.5 kcal/mol (Δ s°, measured using [³H]GBR 1278 @ 25 °C)^{[lower-alpha 42]}

JZ-IV-10 (a "Modafinil hybrid" with cocaine)

Nocaine

Benztropine (3α-Diphenylmethoxy Tropane) Analogs

Benzatropine
Difluoropine (more selective as a DARI than cocaine. Also an anticholinergic & antihistamine)
AHN 1-055 Same structure as for benztropine but 4′,4′-bisfluorinated.
GA 103 N-phenylpropyl bis-4-fluorobenztropine
JHW 007^[26] N-(n-butyl)-3α-[bis(4′-fluorophenyl)methoxy]-tropane

Unlike cocaine & phenyltropanes, the benztropines & GBR compounds (and, as an exception to the cocaine pharmacophore itself, allotropacocaine) among others are considered "atypical" DAT re-uptake pump ligands because they stabilize the dopamine transporter in an inward-facing or closed-to-out conformation, this contrasts what is considered "cocaine-like" affinity to DAT; which would instead keep DAT stable in an open-to-out conformation. This means the binding of many dopamine reuptake inhibitors is atypical of cocaine's method of binding to DAT and significantly diverges from it.^[27]

"Difluoropine" is not a phenyltropane but actually belongs to the benzatropine family of DRIs. Not to be confused for the "diaryl"-phenyltropanes.

In certain respects these are important because they share SAR overlap with GBR 12909 and related analogs.

SARs have shown that 4′,4′-difluorination is an excellent way to boost DAT activity of benztropine, and gives excellent selectivity over the SERT and the NET.^[28]^[29]

Furthermore, replacing the N-Me with, e.g. n-phenylpropyl helps to bring muscarinic activity down to something that is the same as DRI affinity.^[28]

This is remarkable considering unmodified (native) benztropine is 60 times more active as an anticholinergic than as a dopaminergic.^[28]

M1 receptor considerations aside, analogues of this benztropine class still won't substitute for cocaine, and have no propensity to elevate locomotor activity.

Compound 276

3α-Diphenylmethoxy tropanes
(Benztropine analog affinities binding to DAT & DA uptake)^{[lower-alpha 43]}
S. Singh's alphanumeric assignation (name)	R	R′	K_i (nM) [³H]WIN 35428 binding	IC₅₀ (nM) [³H]DA uptake	Selectivity uptake/binding
(Cocaine)			388 ± 47	-	-
(GBR 12909)			11.6 ± 31	-	-

(Benztropine)	H	H	118 ± 9	403 ± 115	3.4
249a	4′-F	H	32.2 ± 10	48	1.5
249b	4′-F	4′-F	11.8 ± 1	71	6.0
249c	3′,4′-di-F	H	27.9 ± 11	181 ± 45.7	6.5
249d	4′-Cl	H	30.0 ± 12	115	3.8
249e	4′-Cl	4′-Cl	20.0 ± 14	75	3.8
249f	3′,4′-di-Cl	H	21.1 ± 19	47	2.2
249g	3′,4′-di-Cl	F	18.9 ± 14	24	1.3
249h	4′-Br	H	37.9 ± 7	29	0.8
249i	4′-Br	4′-Br	91.6	34	0.4
249j	4′-NO₂	H	197 ± 8	219	1.1
249k	4′-CN	H	196 ± 9	222	1.1
249l	4′-CF₃	H	635 ± 10	2155	3.4
249m	4′-OH	H	297 ± 13	677	2.3
249n	4′-OMe	H	78.4 ± 8	468	6.0
249o	4′-OMe	4′-OMe	2000 ± 7	2876	1.4
249p	4′-Me	H	187 ± 5	512	2.7
249q	4′-Me	4′-Me	420 ± 7	2536	6.0
249r	4′-Et	H	520 ± 8	984	1.9
249s	4′-t-Bu	H	1918	4456	2.3
250a	3′-F	H	68.5 ± 12	250 ± 64.7	3.6
250b	3′-F	3′-F	47.4 ± 1	407 ± 63.9	8.6
250c	3′-Cl	H	21.6 ± 7	228 ± 77.1	10.5
250d	3′-CF₃	H	187 ± 5	457 ± 72.0	2.4
251a	2′-F	H	50.0 ± 12	140 ± 17.2	2.8
251b	2′-Cl	H	228 ± 9	997 ± 109	4.4
251c	2′-Me	H	309 ± 6	1200 ± 1.64	3.9
251d	2′-NH₂	H	840 ± 8	373 ± 117	0.4

3α-Diphenylmethoxy-2β-carbomethoxybenztropine
(Benztropine affinities to DAT & 5-HTT in cynomologous monkey caudate-putamen)^{[lower-alpha 44]}
S. Singh's alphanumeric assignation (name)	R	R′	IC₅₀ (nM) DAT (Binding of [³H]WIN 35428)	IC₅₀ (nM) 5-HTT (Binding of [³H]Citalopram)	Selectivity 5-HTT/DAT
(benztropine)			312 ± 1.1	24100 ± 14800	77.2
(WIN 35428)			12.9 ± 1.1	160 ± 20	12.4
R-256			2040 ± 283	1460 ± 255	0.7

S-257a	H	H	33.5 ± 4.5	10100 ± 1740	301
S-257b	H	F	13.2 ± 1.9	4930 ± 1200	373
S-257c (difluoropine)	F	F	10.9 ± 1.2	3530 ± 1480	324
S-257d	H	Cl	15.8 ± 0.95	5960 ± 467	377
S-257e	Cl	Cl	91.4 ± 0.85	3360 ± 1480	36.8
S-257f	H	Br	24.0 ± 4.6	5770 ± 493	240
S-257g	Br	Br	72.0 ± 3.65	2430 ± 339	33.7
S-257h	H	I	55.9 ± 10.3	9280 ± 1640	166
S-257i	Br	I	389 ± 29.4	4930 ± 82	12.7
S-257j	I	I	909 ± 79	8550 ± 442	9.4
S-257k	H	Me	49.5 ± 6.0	13200	266
S-257l	Me	Me	240 ± 18.4	9800 ± 2680	40.8

Compound 277

N-Modified 2-carbomethoxybenztropines
(Benztropine affinities to DAT & 5-HTT in cynomologous monkey caudate-putamen)^{[lower-alpha 45]}
S. Singh's alphanumeric assignation (name)	R	n	IC₅₀ (nM) DAT (Binding of [³H]WIN 35428)	IC₅₀ (nM) 5-HTT (Binding of [³H]Citalopram)	Selectivity 5-HTT/DAT

258a			20.3 ± 3.5	-	-
258b	H	₁	223 ± 53	4970 ± 700	22.3
258c	H	₃	22.0 ± 11.9	19.7 ± 3	0.9
258d	Br	₃	80.2 ± 8.8	234 ± 0.5	2.9
258e	I	₃	119 ± 11	2200 ± 1250	18.5
258f	H	₅	99.0 ± 28	550 ± 63	5.5
259			616 ± 88	55200 ± 20000	89.3

N-substituted 3α[bis(4′-fluorophenyl)methoxy]tropanes
(Benztropine affinities to DAT & 5-HTT)^{[lower-alpha 46]}
S. Singh's alphanumeric assignation (name)	R	K_i (nM) DAT (Binding of [³H]WIN 35428)	IC₅₀ (nM) 5-HTT (Uptake of [³H]DA)	Selectivity uptake/binding

260	H	11.2 ± 11	9.7	0.9
261a	3-phenylpropyl	41.9 ± 11	230	5.5
261b	indole-3-ethyl	44.6 ± 11	1200	26.9
261c	4-phenylbutyl	8.51 ± 14	39	4.6
261d	4-(4′-nitrophenyl)butyl	20.2 ± 11	650	32.2
261e	3-(4′-fluorophenyl)propyl	60.7 ± 12	-	-
262a	n-butyl	24.6 ± 8	370	15.0
262b	cyclopropylmethyl	32.4 ± 9	180	5.5
262c	allyl	29.9 ± 10	14	0.5
262d	benzyl	82.2 ± 15	290	3.5
262e	4-fluorobenzyl	95.6 ± 10	200	2.1
262f	cinnanyl	86.4 ± 12	180	2.1
262g	[bis(4-fluorophenyl)methoxy]ethyl	634 ± 23	-	-
262h	[(4-nitrophenyl)phenylmethoxy]ethyl	57.0 ± 17	-	-
263	acetyl	2340	4600	2.0
264	formyl	2020 ± 13	5400	2.7
265a	Ts	0%^ɑ	-	-
265b	Ms	18%^ɑ	-	-
266		108 ± 12	130	1.2

^ɑInhibition at 10 µM

8-Oxa-2-carbomethoxy norbenztropines
(8-Oxanortropane benztropine analog affinities to DAT & 5-HTT)^{[lower-alpha 47]}
S. Singh's alphanumeric assignation (name)		IC₅₀ (nM) DAT (Binding of [³H]WIN 35428)	IC₅₀ (nM) 5-HTT (Binding of [³H]Citalopram)
R/S-268	2β,3β	>10000	>1660
R/S-269	2α,3β	20300	>1660
R/S-270	2α,3α	22300	>1660
R/S-271	2β,3α	520	>1660

Bicyclic Amine Analogues

EXP-561

Quinuclidine Analogues

Butyltolylquinuclidine

Miscellaneous loosely analogous stimulants

Strobamine, a DARI functional cocaine analog.^[30]

Benzoates (Structures with both stimulant & local anesthetic effects)

Dimethocaine/Larocaine (DMC) (An aniline)
Nitracaine

See some of Robert Clarke's contributions

Chromen-2-one

US 2011136854
Compound	DA-uptake IC₅₀(μM)	NA-uptake IC₅₀(μM)	5-HT-uptake IC₅₀(μM)
7-(((1R,3r,5S)-9-Azabicyclo[3.3.1]nonan-3-yl)oxy)-2H-chromen-2-one	0.0013	0.24	0.076
7-(((1R,3r,5S)-9-Methyl-9-azabicyclo[3.3.1]nonan-3-yl)oxy)-2H-chromen-2-one	0.0029	0.15	0.27

Organochlorides

Org 6582
A potent and long-lasting monoamine re-uptake inhibitor used in drug research.

2,3-Benzodiazepines

GYKI-52895

Phenethylamines

Methylenedioxypyrovalerone: Prolintane: α-Pyrrolidinopropiophenone:

Many phenethylamines are dopamine releasers, however, certain drugs of the family inhibit dopamine reuptake & transport which may be loosely classed as cocaine analogs. Dependent upon their specific configurations.

Adamantanes

Spirocyclic tropanyl-Δ(2)-isoxazoline compound: 3′-methoxy-8-methyl-spiro(8-azabicyclo(3.2.1)octane-3,5′(4′H)-isoxazole which allosterically enhances SERT binding of other reuptake ligands.^[31]

A-77636

Bromantane

Pyridines

Altinicline

Nicotinic agonist which stimulates the release of dopamine.

Naphthyridines

Desmethoxyyangonin (5,6-dehydrokawain), reversible MAO-B inhibitor believed to contribute to mediating dopamine release in nucleus accumbens.

Amfonelic acid

Being a carboxylic acid, amfonelic acid could potentially be used as a carboxylate for the protonation to the free base of another compound; even conceivably creating a 'cocaine amfonelate' or 'cocaine AFA' as opposed to cocaine HCl, cocaine citrate or cocaine HBr et cetera wherein such a case it's conjugate used to form it as a salt would additionally be dopaminergic.

Quinazolinamines (Allosteric functional DAT reuptake inhibitors)

cf. the benztropine phenyltropanes:

SoRI-20041 is a functional, but not structural, cocaine analog which violates traditional structure analog categorization in its case that it has an entirely other binding site. It is however an analog to cocaine in the sense that it functions as a partial DARI on DAT, although doing so when said DAT is compromised by amphetamine-type mediated release of DA. Something unaugmented cocaine cannot do. It nevertheless performs the role of an analogous adjunct to cocaine's function for phosphorylated DAT. It is however worth noting that as for its structure, it displays a certain degree of shared conformation with the benztropine phenyltropanes.

Piperazines (Aryl-1,4-dialkyl piperazines)

GBR-13098: 281 (decanoate 5):

GBR compounds were derived from the benztropines by replacing their tropane nucleus with a piperazine ring (and therefore constitute being congeners with cocaine).^{[lower-alpha 48]} The name "GBR" is derived from its maker Gist-Brocades (now DSM), Netherlands.

GBR 12783 analogues inhibition of DAT binding & DA uptake^{[lower-alpha 49]}
S. Singh's alphanumeric assignation (name)	R	K_i (nM) [³H]WIN 35425	IC₅₀ (nM) [³H]DA	Selectivity uptake/binding
(Cocaine)		224 ± 3.4	208 ± 7.4	0.93
(WIN 35428)		24 ± 3.1	14 ± 1.8	0.58
(DA)		10000 ± 2400	44 ± 5.3	0.004
279 (GBR 12909/Vanoxerine)		27 ± 4.1	0.21 ± 0.06	0.007
282 (GBR 12783)	H	12 ± 1.2^ɑ	-	-

284a	3-NH₂	12 ± 1.0	7 ± 3.5	0.58
284b	3-NCS	160 ± 17	106 ± 37	0.67
284c	4-NH₂	11 ± 0.7	1.6 ± 0.2	0.14
284d	4-NO₂	26 ± 9.3	2.7 ± 0.1	0.10
284e	4-NCS	159 ± 12	26 ± 1.8	0.16
284f	4-maleimide	2327 ± 1000	476 ± 61	0.20

^ɑIC₅₀ for inhibiting [³H]methylphenidate

GBR analogue compounds with piperazine ring-alterations. Binding affinities and inhibition of uptake for DA & 5-HT.^{[lower-alpha 50]}
S. Singh's alphanumeric assignation (name)	R	X-Y (289-290) R₁ (298)	IC₅₀ (nM) [³H]GBR 12935 binding	IC₅₀ (nM) [³H]DA uptake	IC₅₀ (nM) [³H]5-HT uptake	Selectivity [³H]DA uptake/DAT binding	Selectivity [³H]5-HT/[³H]DA uptake
(Cocaine)			660 ± 30 (K_i value)	478 ± 25	304 ± 10	0.72	0.64
(GBR 12935)			4.1 ± 0.6	3.7 ± 0.4	289 ± 29	0.90	78.1
279 (GBR 12909)			5.5 ± 0.4	4.3 ± 0.3	73 ± 1.5	0.78	17.0

289a	H	C-C	21 ± 1.0	9.6 ± 1.5	1720 ± 70	0.46	179
289b	F	C-C	40 ± 1	15 ± 2	459 ± 26	0.37	30.6
(-)289b (2S,5R)	F	C-C	3.6 ± 0.14	8.1 ± 0.3	-	2.25	-
(+)289b (2R,5S)	F	C-C	125 ± 7.0	87 ± 4.1	-	0.70	-
289c	H	C=C	103 ± 13	20 ± 4	2680 ± 122	0.19	134
289d	F	C=C	23 ± 3	28 ± 5	1180 ± 404	1.22	42.1

290a (LR1111)	H	C-C	7.9 ± 1.7	7.2 ± 0.5	34100 ± 359	0.91	4736
290b	F	C-C	4.4 ± 0.4	3.4 ± 0.4	112 ± 24	0.77	32.9
290c	H	C=C	8.6 ± 1.1	0.6 ± 0.1	503 ± 103	0.07	838
290d	F	C=C	2.6 ± 0.4	3.4 ± 0.4	234 ± 10	1.31	68.8
291			286 ± 8	87 ± 5	3150 ± 491	0.30	36.2
292			864 ± 91	93 ± 6	1590 ± 60	0.11	17.1
293			27 ± 4	18 ± 1	2450 ± 57	0.67	136
294			169 ± 5	83 ± 7	1890 ± 268	0.49	22.8
295			80 ± 6	35 ± 2	376 ± 19	0.44	10.7
296			74 ± 5	57 ± 10	2860 ± 45	0.77	50.2
297			20 ± 0.7	9.3 ± 1.8	1480 ± 69	0.46	159

(-)298a	H	H	5.1 ± 0.4	0.7 ± 0.05	986 ± 34	0.14	1409
(+)298a	H	H	747 ± 163	127 ± 10	3210 ± 450	0.17	25.3
(-)298b	F	H	104 ± 8	29 ± 2	20100 ± 2400	0.28	693
(-)298c	H	OH	222 ± 13	31 ± 0.1	857 ± 17	0.14	27.6

Heteroaromatic and fused ring GBR analogue affinities reuptake inhibition for DA & 5-HT and [¹²⁵I]RTI-55 labeled DAT & 5-HTT binding affinities.^{[lower-alpha 51]}
S. Singh's alphanumeric assignation (name)	R	R₁	IC₅₀ (nM) [¹²⁵I]RTI-55 binding DAT	IC₅₀ (nM) [¹²⁵I]RTI-55 binding 5-HTT	IC₅₀ (nM) reuptake [³H]DA	IC₅₀ (nM) reuptake [³H]5-HT	Selectivity binding 5-HTT/DAT	Selectivity uptake [³H]5-HT/[³H]DA
(GBR 12935)	C₆H₅		3.7 ± 0.3	623 ± 13	3.7 ± 0.4	298 ± 29	168	80.5

304a	2-thienyl		5.2 ± 0.3	842 ± 30	9.7 ± 0.2	1990 ± 58	162	205
304b	2-furyl		6.5 ± 0.2	1520 ± 47	8.5 ± 0.5	2550 ± 87	34	300
304c	2-pyridyl		78 ± 4	2420 ± 65	70 ± 6	3700 ± 148	31.0	52.8
279 (GBR 12909)	C₆H₅		3.7 ± 0.4	126 ± 5	7.3 ± 0.2	73 ± 2	34.0	10.0

305a	2-thienyl		3.3 ± 0.1	105 ± 2	6.1 ± 0.7	335 ± 17	31.8	54.9
305b	2-furyl		5.9 ± 0.3	204 ± 7	7.9 ± 0.5	412 ± 9	34.6	52.1
305c	2-pyridyl		16 ± 0.2	2800 ± 139	20 ± 0.8	6520 ± 293	175	326
282 (GBR 12783)	C₆H₅		-	-	-	-	-	-

306a	2-thienyl		6.4 ± 0.3	1170 ± 31	10 ± 0.7	2020 ± 141	183	202
306b	2-furyl		5.0 ± 0.3	1840 ± 59	9.6 ± 0.3	2700 ± 136	368	281
306c	2-pyridyl		44 ± 3	2670 ± 66	64 ± 2	3620 ± 179	60.7	56.6
283 (GBR 13069)	C₆H₅		0.9 ± 0.1	135 ± 7	11 ± 0.6	576 ± 32	150	52.4

307a	2-thienyl		2.2 ± 0.1	88 ± 2	13 ± 1.4	374 ± 17	40.0	28.8
307b	2-furyl		1.8 ± 0.3	109 ± 4	7.2 ± 0.4	442 ± 23	60.5	61.4
307c	2-pyridyl		13.6 ± 0.2	334 ± 12	14.5 ± 1.9	666 ± 21	24.5	45.9

308a	H	(benzothiophen-2-yl)methyl	18.1 ± 1	2420 ± 109	19 ± 1	3520 ± 289	134	185
308b	F	(benzothiophen-2-yl)methyl	4.1 ± 1.1	495 ± 18	34 ± 2	1230 ± 40	121	36.2

309a	H	(benzofuran-2-yl)methyl	17 ± 0.5	1890 ± 48	22 ± 0.7	3040 ± 213	111	138
309b	F	(benzofuran-2-yl)methyl	6.4 ± 0.2	286 ± 10	18.6 ± 0.6	767 ± 27	44.7	41.2

310a	H	(indol-2-yl)methyl	1.1 ± 0.1	668 ± 39	8.8 ± 0.7	2120 ± 166	607	241
310b	F	(indol-2-yl)methyl	0.7 ± 0.1	119 ± 5	13 ± 0.2	506 ± 23	170	38.9

311a	H	(benzimidazol-2-yl)methyl	46 ± 1	1884 ± 72	37 ± 2	4076 ± 221	41.0	110
311b	F	(benzimidazol-2-yl)methyl	15 ± 0.2	256 ± 7	20 ± 0.8	797 ± 43	17.1	39.8

312a	H	(quinolin-2-yl)methyl	199 ± 5	1990 ± 5	192 ± 8	4120 ± 212	10.0	21.5
312b	F	(quinolin-2-yl)methyl	56 ± 1	51 ± 16	106 ± 12	339 ± 31	0.9	3.2

313a	H	(quinolin-3-yl)methyl	72 ± 2	1160 ± 27	111 ± 3	3040 ± 252	16.1	27.4
313b	F	(quinolin-3-yl)methyl	16 ± 3	485 ± 16	74 ± 3	851 ± 36	30.3	11.5

314a	H	(quinolin-6-yl)methyl	190 ± 6	845 ± 15	140 ± 4	1640 ± 58	4.4	11.7
314b	F	(quinolin-6-yl)methyl	62 ± 2	551 ± 21	73 ± 3	1040 ± 46	8.9	14.2

315a	H	3-(benzimidazol-2-yl)propyl	23 ± 0.5	309 ± 9	17 ± 0.7	627 ± 12	13.4	36.9
315b	F	3-(benzimidazol-2-yl)propyl	2.5 ± 0.1	28 ± 2	8.1 ± 0.3	74 ± 4	11.2	9.1

316a	H	(naphthalen-2-yl)methyl	43 ± 2	903 ± 47	32 ± 0.6	926 ± 33	21.0	28.9
316b	F	(naphthalen-2-yl)methyl	8.0 ± 0.3	312 ± 15	30 ± 1	588 ± 39	39.0	19.6

317a	H	(naphthalen-1-yl)methyl	114 ± 5	336 ± 22	406 ± 11	83 ± 5	2.9	0.2
317b	F	(naphthalen-1-yl)methyl	31 ± 1	243 ± 6	312 ± 19	257 ± 12	7.8	0.8

318a	H	2-(naphthalen-1-yl)ethyl	92 ± 13	462 ± 17	42 ± 0.9	578 ± 17	5.0	13.8
318b	F	2-(naphthalen-1-yl)ethyl	7.8 ± 0.2	46 ± 1	25 ± 0.8	119 ± 4	5.9	4.8

Piperidine analogues of piperazine GBR compounds & their affinity to bind at DAT & 5-HTT^{[lower-alpha 52]}
S. Singh's alphanumeric assignation (name)	R	R′	R″	IC₅₀ (nM) DAT [³H]WIN 35428	IC₅₀ (nM) 5-HTT [³H]citalopram	Selectivity 5-HTT/DAT
279 (GBR 12909)				14.0 ± 0.6	82 ± 4	5.8
320 (O-549)				595 ± 148	38 ± 127	0.6

321 (O-526)	F			24.9 ± 3.23	248 ± 72	9.9
322a	H			12.0 ± 0.4	232 ± 28	19.3
322b	Cl			65.0 ± 12	224 ± 10	3.4
322c	Br			159 ± 56	835 ± 142	5.2
322d	OCH₃			255 ± 32	340 ± 24	1.3

323a	H			10.6 ± 0.85	102 ± 5	9.6
323b	F			19.9 ± 9.5	31.9 ± 7.1	1.6
323c	Cl			115 ± 22	414 ± 32	3.6
323d	Br			382 ± 167	638 ± 71	1.7
323e	CH₃			311 ± 71	888 ± 58	2.8

324a	H			15.2 ± 2.8	743 ± 6	48.9
324b	F			9.7 ± 0.4	198 ± 7	20.4

325a	H			14.5 ± 1.9	58 ± 7	3.7
325b	F			13.0 ± 2.5	112 ± 4	8.6

326a	H			108 ± 14	456 ± 90	4.2
326b	F			13.5 ± 2.6	237 ± 53	17.5

327a	H			702 ± 34	544 ± 91	0.8
327b	F			126 ± 13	761 ± 101	6.0

328a	H	H	F	17.2 ± 4.7	1920 ± 233	111.6
328b	H	H	Cl	24.7 ± 5.5	1610 ± 119	65.2
328c	H	H	Br	31.1 ± 2.9	1490 ± 319	47.9
328d	H	Cl	Cl	85.7 ± 4.7	2880 ± 281	33.6
328e	H	H	OCH₃	27.8 ± 6.8	1240 ± 342	44.6
328f	Cl	H	F	52.4 ± 7.8	1810 ± 107	34.5
328g	F	H	F	14.0 ± 3.3	1260 ± 72	90.0
328h	H	H	CH₃	23.0 ± 3.7	1390 ± 240	60.4
328i	H	Cl	F	28.2 ± 3.1	2530 ± 50	89.7
328j	H	H	NO₂	16.4 ± 3.0	1770 ± 305	107.9
328k	H	H	NH₂	101 ± 13	1570 ± 201	15.5

329a	Ph	3-pyridyl		48.6 ± 8.4	680 ± 12.0	14.0
329b	Ph	2-benzo[b]thiophenyl		172 ± 16.4	1540 ± 251	8.9
329c	Ph	2-thienyl		59.3 ± 5.8	1250 ± 87	21.1
329d	2-thienyl	Ph		27.2 ± 0.1	741 ± 108	27.2
329e	2-thienyl	4-F-Ph		13.8 ± 3.4	1390 ± 243	101
329f	2-thienyl	3-pyridyl		58.3 ± 5.7	927 ± 34	15.9

330a	F	4-F-Ph		15.1 ± 2.0	75.8 ± 22.1	5.0
330b	F	Ph		41.4 ± 8.0	271 ± 18.4	6.5
330c	H	Ph		10.1 ± 1.6	231 ± 4.5	22.9
330d	H	4-F-Ph		10.8 ± 3.2	205 ± 13.3	19.0
330e	H	2-thienyl		9.8 ± 2.4	290 ± 63	29.6

331a	Ph	H	4-F-Ph	6.6 ± 1.4	223 ± 32.3	33.8
331b	Ph	H	3-pyridyl	29.9 ± 0.3	194 ± 20.1	6.5
331c	2-thienyl	H	Ph	6.0 ± 0.5	180 ± 21.6	30.0
331d	2-thienyl	F	Ph	11.7 ± 1.0	85.7 ± 2.6	7.3

332a	H	F		9.4 ± 2.6	585 ± 101	62.2
332b	F	H		-	-	-

Dihydroimidazoles

Possible substitutions of the Mazindol molecular structure.

See: List of Mazindol analogues

Mazindol is usually considered a non-habituating (in humans, and some other mammals, but is habituating for e.g. Beagles^{[lower-alpha 53]}) tetracyclic dopamine reuptake inhibitor (of somewhat spurious classification in the former).

It is a loosely functional analog used in cocaine research; due in large part to N-Ethylmaleimide being able to inhibit approximately 95% of the specific binding of [³H]Mazindol to the residues of the MAT binding site(s), however said effect of 10 mM N-Ethylmaleimide was prevented in its entirety by just 10 μM cocaine. Whereas neither 300 μM dopamine or D-amphetamine afforded sufficient protection to contrast the efficacy of cocaine.^{[lower-alpha 54]}

The above steps in its synthesis show the similitude of its precursors to the MAT reuptake inhibitor pipradrol & related compounds.

Local anesthetics (not usually CNS stimulants)

Amylocaine, or Stovaine (above), the first synthetically constructed local anesthetic. Compare structure to dimethylaminopivalophenone (below), an analgesic (opioid). Interestingly, cocaine's classification as a narcotic under U.S. legal code, as has been stretched to be medicinally rationalized such when defining terms very broadly (due to its topical numbing affect, hindering pain signals from CNS recognition via local anesthesia) usually considered an exaggeration of traditional medicine naming convention, in this instance between the first synthetic sodium channel blocker and one of the very simplest opioids there remains a measure of apparent structural similarity between the former anesthetic and latter analgesic "narcotics"; despite the highly differing methods of action for the respective 'pain-killing' properties of either.^[32]

β-Eucaine (Betacain)

In animal studies, certain of the local anesthetics have displayed residual dopamine reuptake inhibitor properties,^[33] although not normally ones that are easily available. These are expected to be more cardiotoxic than phenyltropanes. For example, dimethocaine has behavioral stimulant effects (and therefore not here listed below) if a dose of it is taken that is 10 times the amount of cocaine. Dimethocaine is equipotent to cocaine in terms of its anesthetic equivalency.^[33]

List of local anesthetics
Name	Other common names
Amylocaine	Stovaine
Articaine	Astracaine, Septanest, Septocaine, Ultracaine, Zorcaine
Benzocaine
Bupivacaine	Marcaine, Sensorcaine, Vivacaine
Butacaine
Carticaine
Chloroprocaine	Nesacaine
Cinchocaine/Dibucaine	Cincain, Cinchocaine, Nupercainal, Nupercaine, Sovcaine
Cyclomethycaine	Surfacaine, Topocaine
Etidocaine
Eucaine	α-eucaine, ß-eucaine
Hexylcaine	Cyclaine, Osmocaine
Levobupivacaine	Chirocaine
Lidocaine/Lignocaine	Xylocaine, Betacaine
Mepivacaine	Carbocaine, Polocaine
Meprylcaine/Oracaine	Epirocain
Metabutoxycaine	Primacaine
Phenacaine/Holocaine
Piperocaine	Metycaine
Pramocaine/Pramoxine
Prilocaine	Citanest
Propoxycaine/Ravocaine
Procaine/Novocaine	Borocaine (Procaine Borate), Ethocaine
Proparacaine/Alcaine
Quinisocaine	Dimethisoquin
Risocaine
Ropivacaine	Naropin
Tetracaine/Amethocaine	Pontocaine, Dicaine
Trimecaine	Mesdicain, Mesocain, Mesokain

Analogues for other purposes

Tropanes (Non-ecgonine)

Benzamides

Mefexamide is not a benzamide, but it has structure that is related and is described as a central stimulant, and therefore more correctly a "functional analog". cf. the benzoate stimulants

Procainamide (also an aniline, like dimethocaine)

Toxins

Cocaine to Anatoxin-a:^[34]

Anatoxin-a, also known as "Very Fast Death Factor" (VFDF), is an acutely toxic cyanotoxin with a method of action as an agonist of acetylcholine via those nicotinic class of receptors. Cocaine can be used as a precursor in its synthesis.

VFDF Note its eight, instead of seven, sides (not counting the nitrogen-bridge inside ring)	cf. methylecgonidine, a pyrolysis product of cocaine freebase.	cf. also: ferruginine, a compound even more analogous to the former.^[35]

Notes (inclu. specific locations of citations from within references used)

↑ ^[1] ←Page #969 (45th page of article) §III. ¶1. Final line. Last sentence.
↑ ^[1] ←Page #1,018 (94th page of article) 2nd column, 2nd paragraph.
↑ ^[1] ←Page #940 (16th page of article) underneath Table 8., above §4
↑ ^[1] ←Page #970 (46th page of article) Table 27. Figure 29.
↑ ^[1] ←Page #971 (47th page of article) Figure 30. & Page #973 (49th page of article) Table 28.
↑ ^[1] ←Page #982 (58th page of article)
↑ ^[1] ←Page #971 (47th page of article) Figure 30 & Page #971 (47th page of article) Figure 30 & Page #973 (49th page of article) Table 28
↑ ^[1] ←Page #972 (48th page of article) ¶2, Line 10.
↑ ^[1] ←Page #971 (47th page of article) Figure 30 & Page #971 (47th page of article) Figure 30 & Page #973 (49th page of article) Table 28
↑ ^[1] ←Page #971 (47th page of article) Figure 30 & Page #971 (47th page of article) Figure 30 & Page #973 (49th page of article) Table 28
↑ ^[1] ←Page #971 (47th page of article) Figure 30 & Page #971 (47th page of article) Figure 30 & Page #973 (49th page of article) Table 28
↑ ^[1] ←Page #974 (50st page of article) First (left) column, third ¶
↑ ^[1] ←Page #937 (13th page of article) Second (right) column, first ¶. Above/before §2
↑ ^[1] ←Page #974 (50th page of article) Final ¶ (5th), Second line.
↑ ^[1] ←Page #975 (51st page of article) First ¶, first line.
↑ ^[1] ←Page #975 (51st page of article) First ¶, 4th line.
↑ ^[1] ←Page #973 (49th page of article) §C. & Page #974 (50th page of article) Figure 31 & Page #976 (52nd page of article) Table 29.
↑ ^[1] ←Page #974 (50st page of article) First (left) column, fourth ¶
↑ ^[1] ←Page #974 (50th page of article) Figure 31 & Page #977 (53rd page of article) Table 30.
↑ ^[1] ←Page #974 (50th page of article) Figure 31 & Page #977 (53rd page of article) Table 30.
↑ ^[1] ←Page #974 (50th page of article) Figure 31 & Page #977 (53rd page of article) Table 30.
↑ ^[1] ←Page #974 (50th page of article) Figure 31 & Page #977 (53rd page of article) Table 30.
↑ ^[1] ←Page #978 (54th page of article) §D & Page #980 (56th page of article) Figure 33 & Page #981 (57th page of article) Table 32.
↑ ^[1] ←Page #980 (56th page of article) Scheme 52.
↑ ^[1] ←Page #963 (39th page of article) 2nd (right side) column, 2nd paragraph.
↑ ^[1] ←Page #982 (58th page of article) §G & Page #983 (59th page of article) Figure 36 & Page #984 (60th page of article) Table 35.
↑ ^[1] ←Page #979 (55th page of article) Table 31.
↑ ^[1] ←Page #981 (57th page of article) §E & Page #982 (58th page of article) Table 33.
↑ ^[1] ←Page #970 (46th page of article) §B, 10th line
↑ ^[1] ←Page #971 (47th page of article) 1st ¶, 10th line
↑ ^[1] ←Page #949 (25th page of article) 3rd ¶, 20th line
↑ ^[1] ←Page #982 (58th page of article) 3rd ¶, lines 2, 5 & 6.
↑ ^[1] ←Page #982 (58th page of article) §F, Table 34 & Figure 35.
↑ ^[1] ←Page #984 (60th page of article) §H, Figure 37 & Page #985 (61st page of article) Table 36.
↑ ^[1] ←Page #984 (60th page of article) Scheme 56.
↑ ^[1] ←Page #986 (62nd page of article) §I, Table 37 & Scheme 58
↑ ^[1] ←Page #1,014 (90th page of article) §VIII, A. Figure 59.
↑ ^[1] ←Page #1,016 (92nd page of article) Figure 60.
↑ ^[1] ←Page #990 (66th page of article) Figure 44
↑ ^[24] ←Page #31, §3.2. ¶3, 15th & 16th lines, final sentence.
↑ ^[1] ←Page #927 (3rd page of article) second ¶. Lines seven — fifteen.
↑ ^[1] ←Page #1,006 (82nd page of article) 2nd row, 1st ¶ (orig. ref.: Bonnet, J.-J.; Benmansour, S.; Costenin, J.; Parker, E. M. ;Cubeddu, L. X. J. Pharmacol. Exp. Ther. 1990, 253, 1206)
↑ ^[1] ←Page #987 (63rd page of article) §IV, Figure 39 & Page #988 (64th page of article) Table 38.
↑ ^[1] ←Page #987 (63rd page of article) Figure 40, Page #988 (64th page of article) §B & Page #989 (65th page of article) Table 39.
↑ ^[1] ←Page #987 (63rd page of article) Figure 41, Page #989 (65th page of article) §C & Page #990 (66th page of article) Table 40.
↑ ^[1] ←Page #988 (64th page of article) Figure 42, Page #990 (66th page of article) §2 & Page #992 (68th page of article) Table 41.
↑ ^[1] ←Page #988 (64th page of article) Figure 43, Page #992 (68th page of article) §3 & Table 42.
↑ ^[1] ←Page #993 (69th page of article) §V. ¶2. Fourth line. First sentence.
↑ ^[1] ←Page #993 (69th page of article) §V, Figure 46 & Table 43.
↑ ^[1] ←Page #995 (71st page of article) Figure 47 & Page #997 (73rd page of article) Table 44.
↑ ^[1] ←Page #997 (73rd page of article) §C, Page #998 (74th page of article) Figure 48 & Page #1,000 Table 45.
↑ ^[1] ←Page #1,000 (76th page of article) §D, Page #1,001 (77th page of article) Figure 49 & Page #1,005 (81st page of article) Table 46.
↑ ^[1] ←Page #1,011 (87th page of article) §VII (7) 1st ¶.
↑ ^[1] ←Page #969 (45th page of article) 2nd (right-side) column 2nd ¶.

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↑ Dopamine reuptake transporter (DAT) ``inverse agonism´´ - A novel hypothesis to explain the enigmatic pharmacology of cocaine 2014-12-24 17:08:48 2014-12-25 00:28:27
↑ The binding sites for cocaine and dopamine in the dopamine transporter overlap Nat Neurosci. 2008 Jul; 11(7): 780–789. doi: 10.1038/nn.2146
↑ Tanda, G; Newman, A; Ebbs, AL; Tronci, V; Green, J; Tallarida, RJ; Katz, JL (2009). "Combinations of Cocaine with other Dopamine Uptake Inhibitors: Assessment of Additivity". J Pharmacol Exp Ther. 330 (3): 802–9. doi:10.1124/jpet.109.154302. PMC 2729796. PMID 19483071.
↑ J Pharmacol Exp Ther. 2013 Jul; 346(1): 2–10. Fig. 1. Published online 2013 Jul. doi: 10.1124/jpet.111.191056
1 2 3 Rothman RB, Baumann MH, Prisinzano TE, Newman AH. Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction. Biochem Pharmacol. 2008 Jan 1;75(1):2-16. doi:10.1016/j.bcp.2007.08.007 PMID 17897630
↑ Runyon SP, Carroll FI. Dopamine transporter ligands: recent developments and therapeutic potential. Curr Top Med Chem. 2006;6(17):1825-43. doi:10.2174/156802606778249775 PMID 17017960
↑ Enantioselective synthesis of strobamine and its analogues Xing Zhang et al. Center for Organic and Medicinal Chemistry, Research Triangle Institute. Issue in Honor of Prof. James M.Cook ARKIVOC 2010 (iv)96-103
↑ A novel spirocyclic tropanyl-Δ²-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake. Bioorg Med Chem 2012 Nov 10;20(21):6344-55. Epub 2012 Sep 10.
↑ From cocaine to ropivacaine: the history of local anesthetic drugs. Ruetsch YA, Böni T, Borgeat A. Curr Top Med Chem. 2001 Aug;1(3):175-82. PMID 11895133
1 2 Wilcox, K.M., Kimmel, H.L., Lindsey, K.P., Votaw, J.R., Goodman, M.M., Howell, L.L. In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys. Synapse, 58: 220-228, 2005. PDF
↑ Wegge, Thomas; Schwarz, Simone; Seitz, Gunther (2000). "A new and efficient synthetic route to enantiopure (+)-anatoxin-a from (−)-cocaine hydrochloride". Tetrahedron: Asymmetry 11 (6): 1405–1410. doi:10.1016/S0957-4166(00)00059-8.
↑ Approaches to the enantioselective synthesis of ferrugine and its analogues Institute of Chemistry, University of Bialystok, ul. Hurtowa 1, 15-339 Bialystok, Poland

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Phenyltropanes (classifications)

2-Carboxymethyl Esters	Troparil WIN 35428 RTI-31 RTI-32 RTI-51 RTI-55 RTI-83

(3,4-Disubstituted Phenyl)-tropanes	Dichloropane RTI-112 RTI-353

Arylcarboxy	RTI-113 RTI-120

Carboxyalkyl	RTI-121 RTI-150

Acyl	PTT/WF-11 WF-23 PIT/WF-21 WF-33

β,α Stereochemistry	RTI-352 RTI-274

α,β Stereochemistry	Brasofensine Tesofensine NS2359

Heterocycles: 3-Substituted-isoxazol-5-yl	RTI-177 RTI-336 RTI-371

Heterocycles: 3-Substituted-1,2,4-oxadiazole	RTI-126 RTI-371

N-alkyl	FP-β-CPPIT FE-β-CPPIT Altropane Ioflupane (¹²³I)

N-replaced (S,O,C)	Tropoxane

Irreversible	RTI-76

Nortropanes (N-demethylated)	NS2359 (GSK-372,475)

Stimulants (N06B)

Adamantanes	Adaphenoxate Adapromine Amantadine Bromantane Chlodantane Gludantane Memantine Rimantadine

Adenosine antagonists	8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Paraxanthine SCH-58261 Theobromine Theophylline

Alkylamines	Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane

Ampakines	CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram

Arylcyclohexylamines	Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine

Benzazepines	6-Br-APB SKF-77434 SKF-81297 SKF-82958

Cholinergics	A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538

Convulsants	Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone

Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol JZ-IV-10 Modafinil

Oxazolines	4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone

Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Phenyl-2-(piperidin-1-yl)pentan-3-one 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fuoroamphetamine 2-Fuoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2-Phenyl-3-methylaminobutane 2,3-MDA 3-Fuoroamphetamine 3-Fluoroethamphetamine 3-Fluoromethcathinone 3-Methoxyamphetamine 3-Methylamphetamine 3,4-DMMC 4-BMC 4-CMC 4-Ethylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-Methylbuphedrone 4-Methylcathinone 4-MMA 4-Methylpentedrone 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amfepramone Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzedrone Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Buphedrone Bupropion Butylone Camfetamine Cathine Cathinone Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dimethylcathinone Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethcathinone Ethylnorepinephrine Ethylone Etilamfetamine Etilefrine Famprofazone Fencamfamine Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Flephedrone Fludorex Formetorex Furfenorex Gepefrine Hexapradol HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine IMP Indanylamphetamine Iofetamine Isoetarine Isoethcathinone Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA MDBU MDEA MDMA MDMPEA MDOH MDPR MDPEA Mefenorex Mephedrone Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methcathinone Methedrone Methoxyphenamine Methylenedioxycathinone Methylone Mexedrone MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N-Benzyl-1-phenethylamine N-Ethylbuphedrone N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine (drug) Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Pentedrone Pentylone Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Phthalimidopropiophenone Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine

Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine

Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 MeOPP MBZP Vanoxerine

Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 1-(3,4-Dichlorophenyl)-1-(piperidin-2-yl)butane 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3-Chloromethylphenidate 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate Methylphenidate (Dexmethylphenidate) N-Methyl-3β-propyl-4β-(4-chlorophenyl)piperidine Nocaine Phacetoperane Pipradrol Propylphenidate SCH-5472

Pyrrolidines	2-Diphenylmethylpyrrolidine 5-DBFPV α-PPP α-PBP α-PHP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone

Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide

Tropanes	3-CPMT 3'-Chloro-3a-(diphenylmethoxy)tropane 4-fluorotropacocaine 4'-Fluorococaine AHN-1055 Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (¹²³I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-105 RTI-112 RTI-113 RTI-117 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-154 RTI-171 RTI-177 RTI-183 RTI-193 RTI-194 RTI-199 RTI-202 RTI-204 RTI-229 RTI-241 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33 WF-60

Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT

Others	2-MDP 2-Phenylcyclohexylamine 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Levopropylhexedrine Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 Propylhexedrine PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine

Category Index Outline Portal

Serotonergics

5-HT₁ receptor ligands

5-HT_1A

Agonists: 8-OH-DPAT Adatanserin Amphetamine Antidepressants (e.g., etoperidone, nefazodone, trazodone, vilazodone, vortioxetine) Atypical antipsychotics (e.g., aripiprazole, asenapine, clozapine, lurasidone, quetiapine, ziprasidone) Azapirones (e.g., buspirone, eptapirone, gepirone, perospirone, tandospirone) Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Dopamine Ebalzotan Eltoprazine Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, lisuride, LSD, methylergometrine (methylergonovine), methysergide, pergolide) F-11461 F-12826 F-13714 F-14679 F-15063 F-15599 Flesinoxan Flibanserin Flumexadol Lesopitron LY-293284 LY-301317 mCPP MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24969 S-14506 S-14671 S-15535 Sarizotan Serotonin (5-HT) SSR-181507 Sunepitron Tryptamines (e.g., 5-CT, 5-MeO-DMT, 5-MT, bufotenin, DMT, indorenate, N-Me-5-HT, psilocin, psilocybin) TGBA01AD U-92016A Urapidil Vilazodone Xaliproden Yohimbine

Antagonists: Atypical antipsychotics (e.g., iloperidone, risperidone, sertindole) AV965 Beta blockers (e.g., alprenolol, cyanopindolol, iodocyanopindolol, oxprenolol, pindobind, pindolol, propranolol, tertatolol) BMY-7378 CSP-2503 Dotarizine Ergolines (e.g., metergoline) Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine (methiothepin) MIN-117 (WF-516) MPPF NAN-190 Robalzotan S-15535 SB-649915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100135 WAY-100635 Xylamidine

Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine))

5-HT_1B

Agonists: CGS-12066A CP-93129 CP-94253 CP-122,288 CP-135807 Eltoprazine Ergolines (e.g., bromocriptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) mCPP RU-24969 Serotonin (5-HT) Triptans (e.g., avitriptan, donitriptan, eletriptan, sumatriptan, zolmitriptan) TFMPP Tryptamines (e.g., 5-BT, 5-CT, 5-MT, DMT) Vortioxetine

Antagonists: AR-A000002 Elzasonan Ergolines (e.g., metergoline) GR-127935 Isamoltane LY-393558 Metitepine (methiothepin) SB-216641 SB-224289 SB-236057 Yohimbine

Unknown/unsorted: Ergolines (e.g., cabergoline, ergometrine (ergonovine), lisuride)

5-HT_1D

Agonists: CP-122,288 CP-135807 CP-286601 Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, LSD, methysergide) GR-46611 L-694247 L-772405 mCPP PNU-109291 PNU-142633 Serotonin (5-HT) TGBA01AD Triptans (e.g., almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) Tryptamines (e.g., 5-BT, 5-CT, 5-Et-DMT, 5-MT, 5-(nonyloxy)tryptamine, DMT)

Antagonists: Alniditan BRL-15572 Elzasonan Ergolines (e.g., metergoline) GR-127935 Ketanserin LY-310762 LY-367642 LY-393558 LY-456219 LY-456220 Metitepine (methiothepin) Mianserin Ritanserin Yohimbine Ziprasidone

Unknown/unsorted: Ergolines (e.g., lisuride, lysergol, pergolide)

5-HT_1E

Agonists: BRL-54443 Ergolines (e.g., methysergide) Serotonin (5-HT) Triptans (e.g., eletriptan) Tryptamines (e.g., tryptamine)

Antagonists: Metitepine (methiothepin)

Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine), lysergol, methylergometrine (methylergonovine)

5-HT_1F

Agonists: BRL-54443 CP-122,288 Ergolines (e.g., bromocriptine, lysergol, methylergometrine (methylergonovine) methysergide) Lasmiditan LY-334370 Serotonin (5-HT) Triptans (e.g., eletriptan, naratriptan, sumatriptan) Tryptamines (e.g., 5-MT)

Antagonists: Mianserin Metitepine (methiothepin)

5-HT₂ receptor ligands

5-HT_2A

Agonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN-NBOH, 2CBFly-NBOMe) 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 2C-B-FLY 2CB-Ind 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) AL-34662 AL-37350A Bromo-DragonFLY Dimemebfe DMBMPP DOx (e.g., DOB, DOC, DOI, DOM) Efavirenz Ergolines (e.g., 1P-LSD, ALD-52, bromocriptine, cabergoline, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, methylergometrine (methylergonovine), pergolide) Flumexadol Jimscaline Lorcaserin MDxx (e.g., MDA, MDMA, MDOH, MMDA) O-4310 Oxaflozane PHA-57378 PNU-22394 PNU-181731 RH-34 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., BZP, mCPP, quipazine, TFMPP) Serotonin (5-HT) TCB-2 TFMFly Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)

Antagonists: 5-I-R91150 5-MeO-NBpBrT AC-90179 Adatanserin Altanserin AMDA APD-215 Atypical antipsychotics (e.g., amperozide, aripiprazole, asenapine, blonanserin, carpipramine, clocapramine, clorotepine, clozapine, fluperlapine, gevotroline, iloperidone, melperone, mosapramine, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zicronapine, ziprasidone, zotepine) Cinanserin CSP-2503 Cyproheptadine Deramciclane Dotarizine Eplivanserin Ergolines (e.g., amesergide, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole) Etoperidone Fananserin Flibanserin Glemanserin Irindalone Ketanserin KML-010 Lubazodone LY-393558 Medifoxamine Mepiprazole Metitepine (methiothepin) MIN-101 Nantenine Nefazodone Phenoxybenzamine Pimavanserin Pirenperone Pizotifen Pruvanserin Rauwolscine Ritanserin S-14671 Sarpogrelate Setoperone Spiperone Spiramide SR-46349B TGBA01AD Teniloxazine Temanogrel Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) Trazodone Tricyclic antidepressants (e.g., amitriptyline) Typical antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, pimozide, pipamperone, prochlorperazine, thioridazine, thiothixene, trifluoperazine) Volinanserin Xylamidine Yohimbine

Unknown/unsorted: Ergolines (e.g., dihydroergotamine, ergometrine (ergonovine), nicergoline) MIN-117 (WF-516)

5-HT_2B

Agonists: 4-Methylaminorex Aminorex Amphetamines (eg., chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine) BW-723C86 DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., cabergoline, dihydroergocryptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) MDxx (e.g., MDA, MDMA, MDOH, MMDA) Piperazines (e.g., mCPP) PNU-22394 Ro60-0175 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, 5-MT, α-Me-5-HT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)

Antagonists: Agomelatine Asenapine Cyproheptadine EGIS-7625 Ergolines (e.g., amesergide, bromocriptine, lisuride, LY-53857, LY-272015, mesulergine) Ketanserin LY-393558 Metadoxine Metitepine (methiothepin) Pirenperone Propranolol PRX-08066 Rauwolscine Ritanserin RS-127445 Sarpogrelate SB-200646 SB-204741 SB-206553 SB-215505 SB-221284 SB-228357 SDZ SER-082 Tegaserod Tetracyclic antidepressants (e.g., amoxapine, mianserin) TIK-301 Yohimbine

Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine))

5-HT_2C

Agonists: 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) A-372159 AL-38022A Alstonine CP-809101 Dimemebfe DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., ALD-52, cabergoline, dihydroergotamine, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, pergolide) Flumexadol Lorcaserin MDxx (e.g., MDA, MDMA, MDOH, MMDA) MK-212 Org 12962 Org 37684 Oxaflozane PHA-57378 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., aripiprazole, BZP, mCPP, quipazine, TFMPP) PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine) Vabicaserin WAY-629 WAY-161503 YM-348

Antagonists: Adatanserin Agomelatine Atypical antipsychotics (e.g., asenapine, clorotepine, clozapine, fluperlapine, iloperidone, melperone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine) Captodiame CEPC Cinanserin Cyproheptadine Deramciclane Dotarizine Eltoprazine Ergolines (e.g., amesergide, bromocriptine, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole) Etoperidone Fluoxetine FR-260010 Irindalone Ketanserin Ketotifen Latrepirdine (dimebolin) Medifoxamine Metitepine (methiothepin) Nefazodone Pirenperone Pizotifen Propranolol Ritanserin RS-102221 S-14671 SB-200646 SB-206553 SB-221284 SB-228357 SB-242084 SB-243213 SDZ SER-082 Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) TIK-301 Trazodone Tricyclic antidepressants (e.g., amitriptyline, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine, pimozide, pipamperone, thioridazine) Xylamidine

Unknown/unsorted: Efavirenz Ergolines (e.g., ergometrine (ergonovine), methylergometrine (methylergonovine))

5-HT₃

Agonists: Alcohols (e.g., butanol, ethanol, trichloroethanol) m-CPBG Phenylbiguanide Piperazines (e.g., BZP, mCPP, quipazine) RS-56812 Serotonin (5-HT) SR-57227 SR-57227A Tryptamines (e.g., 2-Me-5-HT, 5-CT, bufotenidine (5-HTQ)) Volatiles/gases (e.g., halothane, isoflurane, toluene, trichloroethane) YM-31636

Antagonists: Alosetron AS-8112 Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine) Azasetron Batanopride Bemesetron (MDL-72222) Cilansetron CSP-2503 Dazopride Dolasetron Galanolactone Granisetron ICS-205930 Lerisetron Memantine Ondansetron Palonosetron Ramosetron Renzapride Ricasetron Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Thujone Tropanserin Tropisetron Typical antipsychotics (e.g., loxapine) Volatiles/gases (e.g., nitrous oxide, sevoflurane, xenon) Vortioxetine Zacopride Zatosetron

Unknown/unsorted: LY-53857 Piperazines (e.g., naphthylpiperazine)

5-HT₄

Agonists: 5-MT BIMU8 Capeserod Cinitapride Cisapride CJ-033466 Dazopride Metoclopramide Mosapride Prucalopride PRX-03140 Renzapride RS-67333 RS-67506 Serotonin (5-HT) Tegaserod Velusetrag Zacopride

Antagonists: GR-113808 GR-125487 L-Lysine Piboserod RS-39604 RS-67532 SB-203186 SB-204070

5-HT_5A

Agonists: Ergolines (e.g., 2-Br-LSD (BOL-148), ergotamine, LSD) Serotonin (5-HT) Tryptamines (e.g., 5-CT) Valerenic Acid

Antagonists: Asenapine Latrepirdine (dimebolin) Metitepine (methiothepin) Ritanserin SB-699551 Unknown/unsorted: Ergolines (e.g., metergoline, methysergide) Piperazines (e.g., naphthylpiperazine)

5-HT₆

Agonists: Ergolines (e.g., dihydroergocryptine, dihydroergotamine, ergotamine, lisuride, LSD, mesulergine, metergoline, methysergide) Serotonin (5-HT) Tryptamines (e.g., 2-Me-5-HT, 5-BT, 5-CT, 5-MT, Bufotenin, E-6801, E-6837, EMD-386088, EMDT, LY-586713, N-Me-5-HT, tryptamine) WAY-181187 WAY-208466

Antagonists: ABT-354 Atypical antipsychotics (e.g., aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, iloperidone, olanzapine, tiospirone) AVN-101 AVN-211 AVN-322 AVN-397 BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12233 GW-742457 Idalopirdine Ketanserin Latrepirdine (dimebolin) Metitepine (methiothepin) MS-245 PRX-07034 Ritanserin Ro04-6790 Ro 63-0563 SB-258585 SB-271046 SB-357134 SB-399885 SB-742457 Tetracyclic antidepressants (e.g., amoxapine, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine)

Unknown/unsorted: Ergolines (e.g., 2-Br-LSD (BOL-148), bromocriptine, lergotrile, pergolide) Piperazines (e.g., naphthylpiperazine)

5-HT₇

Agonists: 8-OH-DPAT AS-19 Bifeprunox E-55888 Ergolines (e.g., LSD) LP-12 LP-44 RU-24969 Sarizotan Serotonin (5-HT) Triptans (e.g., frovatriptan) Tryptamines (e.g., 5-CT, 5-MT, bufotenin, N-Me-5-HT)

Antagonists: Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, olanzapine, risperidone, sertindole, tiospirone, ziprasidone, zotepine) Butaclamol DR-4485 EGIS-12233 Ergolines (e.g., 2-Br-LSD (BOL-148), amesergide, bromocriptine, cabergoline, dihydroergotamine, ergotamine, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole) Ketanserin LY-215840 Metitepine (methiothepin) Ritanserin SB-258719 SB-258741 SB-269970 SB-656104 SB-656104A SB-691673 SLV-313 SLV-314 Spiperone SSR-181507 Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, imipramine) Typical antipsychotics (e.g., acetophenazine, chlorpromazine, chlorprothixene, fluphenazine, loxapine, pimozide) Vortioxetine

Unknown/unsorted: Ergolines (e.g., lisuride, pergolide) Piperazines (e.g., naphthylpiperazine)

Reuptake inhibitors

SERT

Selective serotonin reuptake inhibitors (SSRIs): Alaproclate Cericlamine Citalopram Dapoxetine Desmethylcitalopram Escitalopram Femoxetine Fluoxetine Fluvoxamine Indalpine Ifoxetine Omiloxetine Panuramine Paroxetine Pirandamine RTI-353 Seproxetine Sertraline Vilazodone Zimelidine

Serotonin-norepinephrine reuptake inhibitors (SNRIs): Bicifadine BTS-54505 Desvenlafaxine Duloxetine Eclanamine Levomilnacipran McN-5652 Milnacipran N-Methyl-PPPA PPPA Sibutramine Venlafaxine WY-45233

Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs): (S)-Duloxetine 3,3-Diphenylcyclobutanamine Amifitadine Ansofaxine Bicifadine Brasofensine Centanafadine Cocaine Dasotraline Desmethylsertraline Diclofensine DOV-102677 DOV-216303 EXP-561 Fezolamine HDMP-28 Indatraline JNJ-7925476 JZ-IV-10 Liafensine Mazindol Naphyrone Nefazodone Nefopam NS-2359 Perafensine PRC200 SEP-228431 SEP-228432 Tedatioxetine Tesofensine

Tricyclic antidepressants (TCAs): Amitriptyline Butriptyline Cianopramine Clomipramine Desipramine Dosulepin Doxepin Imipramine Lofepramine Nortriptyline Pipofezine Protriptyline Trimipramine

Others: A-80426 Amoxapine Antihistamines (e.g., brompheniramine, chlorphenamine, dimenhydrinate, diphenhydramine, mepyramine (pyrilamine), pheniramine, tripelennamine) Arylcyclohexylamines (e.g., esketamine, ketamine, phencyclidine) CP-39332 Cyclobenzaprine Dextromethorphan Dextrorphan Efavirenz Etoperidone EXP-561 Fezolamine Litoxetine LY-393558 Loxapine Lubazodone Medifoxamine Mesembrine Mifepristone MIN-117 (WF-516) N-Me-5-HT Opioids (e.g., dextropropoxyphene, methadone, pethidine (meperidine), levorphanol) PIM-35 Pridefine Roxindole SB-649915 TGBA01AD Tofenacin Trazodone Tropanes (e.g., cocaine) Vortioxetine Ziprasidone

VMATs

Amiodarone
Amphetamines (e.g., amphetamine, methamphetamine, MDMA)
APP
AZIK
Bietaserpine
Deserpidine
Dihydrotetrabenazine
Efavirenz
GBR-12935
GZ-793A
Ibogaine
Ketanserin
Lobeline
Methoxytetrabenazine
NBI-98854
Reserpine
Rose bengal
SD-809
Tetrabenazine
Vanoxerine (GBR-12909)

Releasing agents

Aminoindanes: 5-IAI AMMI ETAI MDAI MDMAI MMAI TAI

Aminotetralins: 6-CAT 8-OH-DPAT MDAT MDMAT

Oxazolines: 4-Methylaminorex Aminorex Clominorex Fluminorex

Phenethylamines: 2-Methyl-MDA 4-CAB 4-FA 4-FMA 4-HA 4-MTA 5-APDB 5-Methyl-MDA 6-APDB 6-Methyl-MDA AEMMA Amiflamine BDB BOH Brephedrone Butylone Chlorphentermine Cloforex Amfepramone Metamfepramone DCA Dexfenfluramine DFMDA DMA DMMA EBDB EDMA Ethylone Etolorex Fenfluramine Flephedrone Flucetorex IAP IMP Iofetamine Levofenfluramine Lophophine MBDB MDA MDEA MDHMA MDMA MDMPEA MDOH MDPEA Mephedrone Methedrone Methylone MMA MMDA MMDMA MMMA NAP Norfenfluramine 4-TFMA pBA pCA pIA PMA PMEA PMMA TAP

Piperazines: 2C-B-BZP 3-MeOPP BZP DCPP MBZP mCPP MDBZP MeOPP Mepiprazole pCPP pFPP pTFMPP TFMPP

Tryptamines: 4-Methyl-αET 4-Methyl-αMT 5-CT 5-MeO-αET 5-MeO-αMT 5-MT αET αMT DMT Tryptamine

Others: Indeloxazine Tramadol Viqualine

Non-selective: Benmoxin Caroxazone Echinopsidine Furazolidone Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivalylbenzhydrazine Procarbazine Safrazine Tranylcypromine

MAO-A-selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline Eprobemide Esuprone Harmala alkaloids (e.g., harmine, harmaline, harman, norharman, tetrahydroharmine) Methylene blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone Tyrima

Others

Precursors	L-Tryptophan → 5-HTP

Cofactors	Ferrous iron (Fe²⁺) Magnesium (Mg²⁺) Tetrahydrobiopterin Vitamin B₃ (Niacin Nicotinamide → NADPH) Vitamin B₆ (Pyridoxine Pyridoxamine Pyridoxal → Pyridoxal phosphate) Vitamin B₉ (Folic Acid → Tetrahydrofolic acid) Vitamin C (Ascorbic acid) Zinc (Zn²⁺)

Neurotoxins	3-CA 4-CAB 5,7-DHT α-Me-DA (3,4-DHA) αET αMT DCA MDA MDMA PBA PCA PIA

Others	Activity enhancers: BPAP PPAP

See also: Adrenergics
Dopaminergics
Melatonergics

Sigma receptor modulators

Receptor
(ligands)

σ (1, 2)

Agonists	3-MeO-PCE 3-MeO-PCP 3-PPP 4-MeO-PCP 4-IBP 4-PPBP Afobazole Alazocine Amantadine Amitriptyline Arketamine BD-1008 BD1031 BD1052 Berberine Buprenorphine Captodiame Citalopram Clorgiline Cocaine Cutamesine Cyclazocine DHEA DHEA-S Desipramine Dextrallorphan Dextromethorphan Dextrorphan Dimemorfan DMT Donepezil DTG Escitalopram Fluoxetine Fluvoxamine Heroin Ibogaine Igmesine Imipramine JO-1784 Ketamine L-687,384 Lamotrigine Lu 28-179 MDMA Memantine Metaphit Methamphetamine Methoxetamine Methylphenidate Morphine Naluzotan Noscapine OPC-14523 Opipramol PB-28 PD-144,415 Pentazocine Pentoxyverine Phencyclidine PRE-084 Pregnenolone Pregnenolone sulfate Quetiapine RTI-55 SA-4503 Siramesine Tapentadol Tenocyclidine Tramadol UMB23 UMB82 Venlafaxine

Antagonists	AC927 AHD1 AZ66 BD1008 BD1047 BD1060 BD1063 BD1067 BMY-14802 CM156 E-5842 Haloperidol Lamotrigine LR132 LR172 MIN-101 MS-377 Naloxone Naltrexone NE-100 Panamesine PD-144418 Progesterone Rimcazole S1RA (E-52862) Sertraline SM-21 SR-31742A UMB100 UMB101 UMB103 UMB116 YZ-011 YZ-069 YZ-185

Unknown/unsorted	4C-T-2 5-MeO-DiPT 18-MC β-Endopsychosin Chlorpromazine Clemastine Clocapramine Cloperastine D-Deprenyl DiPT DPT Gevotroline Nepinalone Selegiline TMA; Allosteric modulators: SKF-83959

Antiobesity agents/Anorectics (A08)

Central

Stimulants	4-Methylamphetamine^‡ Amfecloral Amfepentorex Amfepramone Aminorex^‡ Amphetamine Amphetaminil Atomoxetine Benfluorex^‡ Benzphetamine Bupropion (+naltrexone; +zonisamide^†) Cathine Cathinone Chlorphentermine Ciclazindol Clobenzorex Cloforex Clominorex Clortermine Dexfenfluramine^‡ Dextroamphetamine Dexmethylphenidate Difemetorex^‡ Dimethylcathinone Diphemethoxidine Ephedrine Ephedra^‡ Etilamfetamine Etolorex Fenbutrazate Fencamfamine Fenethylline Fenfluramine^‡ (+phentermine^‡) Fenproporex Fludorex Fluminorex Furfenorex^‡ Indanorex Khat Levopropylhexedrine Lisdexamfetamine Manifaxine Mazindol Mefenorex Methamphetamine Methylphenidate Norfenfluramine Pemoline Pentorex Phendimetrazine Phenethylamine Phenmetrazine Phentermine (+topiramate) Phenylpropanolamine Picilorex Pipradrol Prolintane Propylhexedrine Pseudoephedrine Pyrovalerone Radafaxine Reboxetine Setazindol Sibutramine^‡ Synephrine Tesofensine Viloxazine Xylopropamine Zylofuramine

Cannabinoid receptor antagonists	Drinabant^§ Ibipinabant^§ Otenabant^§ Rimonabant^‡ Rosonabant^§ Surinabant^§ Taranabant^§

Others	5-HTP Galactomannan Guar gum Glucomannan L-DOPA L-Phenylalanine L-Tryptophan L-Tyrosine Lorcaserin Lu AA-33810 Metformin Naltrexone Naloxone Oxyntomodulin P57 Peptide YY Topiramate Yohimbine (Yohimbe) Zonisamide water

Peripheral

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Antidepressants (N06A)

Specific reuptake inhibitors and/or receptor modulators

SSRIs	Citalopram Escitalopram Fluoxetine^# Fluvoxamine Indalpine^‡ Paroxetine Sertraline Zimelidine^‡

SNRIs	Desvenlafaxine Duloxetine Levomilnacipran Milnacipran Tofenacin Venlafaxine

NRIs	Atomoxetine Reboxetine Viloxazine

NDRIs	Amineptine^‡ Nomifensine^‡

SARIs	Etoperidone Nefazodone^‡ Trazodone

SMSs	Vilazodone Vortioxetine

Others	Agomelatine Amisulpride Amitriptyline/perphenazine Buprenorphine Bupropion Etryptamine^‡ Flupentixol/melitracen Esketamine Ketamine Indeloxazine Lurasidone Medifoxamine^‡ Metryptamine^‡ Olanzapine/fluoxetine Oxaflozane^‡ Quetiapine Tandospirone Teniloxazine Tianeptine Tranylcypromine/trifluoperazine

Tricyclic and tetracyclic antidepressants

TCAs	Amineptine^‡ Amitriptyline^# Amitriptylinoxide Butriptyline^‡ Clomipramine^# Demexiptiline^‡ Desipramine Dibenzepin Dimetacrine^‡ Dosulepin Doxepin Imipramine Imipraminoxide^‡ Iprindole^‡ Lofepramine Melitracen Metapramine^‡ Nitroxazepine Nortriptyline Noxiptiline Opipramol Pipofezine Propizepine^‡ Protriptyline Quinupramine^‡ Tianeptine Trimipramine

TeCAs	Amoxapine Maprotiline Mianserin Mirtazapine Setiptiline

Others	Tiazesim

Monoamine oxidase inhibitors

Non-selective	Irreversible: Benmoxin^‡ Iproclozide^‡ Iproniazid^‡ Isocarboxazid Mebanazine^‡ Nialamide^‡ Octamoxin^‡ Phenelzine Pheniprazine^‡ Phenoxypropazine^‡ Pivhydrazine^‡ Safrazine^‡ Tranylcypromine Reversible: Caroxazone^‡

MAO_A-selective	Reversible: Bifemelane Eprobemide Metralindole Minaprine^‡ Moclobemide Pirlindole Tetrindole Toloxatone

MAO_B-Selective	Irreversible: Selegiline

Adjunctive therapies

Atypical antipsychotics (aripiprazole, lurasidone, olanzapine, quetiapine) Buspirone Lithium (lithium carbonate, lithium citrate) Thyroid hormones (triiodothyronine (T₃), levothyroxine (T₄))

Miscellaneous

Ademetionine (SAMe) Hypericum perforatum (St. John's Wort) Oxitriptan (5-HTP) Tryptophan

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Neuromodulation

Types

♦ Enzyme: Inducer
Inhibitor

♦ Ion channel: Opener
Blocker

♦ Miscellaneous: Precursor
Cofactor

Classes

Enzyme

see Enzyme inhibition

Ion channel

Receptor &
transporter

BA/M

Adrenergic	Adrenergic receptor agonist (α β (1 2)) Adrenergic receptor antagonist (α (1 2), β) Adrenergic reuptake inhibitor (ARI)

Dopaminergic	Dopamine receptor agonist Dopamine receptor antagonist Dopamine reuptake inhibitor (DRI)

Histaminergic	Histamine receptor agonist Histamine receptor antagonist (H₁ H₂ H₃)

Serotonergic	Serotonin receptor agonist Serotonin Receptor Antagonist (5-HT₃) Serotonin reuptake inhibitor (SRI)

GABAergic	GABA receptor agonist GABA receptor antagonist GABA reuptake inhibitor (GRI)

Glutamatergic	Glutamate receptor agonist (AMPA) Glutamate receptor antagonist (NMDA) Glutamate reuptake inhibitor

Cholinergic

Cannabinoidergic

Cannabinoid receptor agonist
Cannabinoid receptor antagonist
Endocannabinoid enhancer (eCBE)
Endocannabinoid reuptake inhibitor (eCBRI)

Opioidergic

Other

Miscellaneous

Cofactor (see Enzyme cofactors)
Precursor (see Amino acids)

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