RTI-83
 | |
| Systematic (IUPAC) name | |
|---|---|
|
methyl (1R,2S,3S,5S)-3-(4-ethylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | |
| Identifiers | |
| CAS Number | 155337-52-3 |
| PubChem | CID 9882384 |
| Chemical data | |
| Formula | C18H25NO2 |
| Molar mass | 287.396 g/mol |
| |
(–)-2β-Carbomethoxy-3β-(4-ethylphenyl)tropane (RTI-4229-83) is a phenyltropane derivative which represents a rare example of an SDRI or serotonin-dopamine reuptake inhibitor, a drug which inhibits the reuptake of the neurotransmitters serotonin and dopamine, while having little or no effect on the reuptake of the related neurotransmitter noradrenaline. With a binding affinity (Ki) of 55 nM at DAT and 28.4 nM at SERT but only 4030 nM at NET, RTI-83 has reasonable selectivity for DAT/SERT over NET
However, further research has shown that by extending the ethyl chain even better selectivity can be achieved, with the 4′-(cis-propenyl) analogue having Ki values of 15 nM at DAT and 7.1 nM at SERT, vs 2800 nM at NET.[1][2] However RTI-436 has an even better selectivity for DAT over NET (3.09nM @ DAT & 1,960nM @ NET or a NET/DAT ratio of 634.3, but with lesser DAT/SERT equivalent potency with a ratio between them of 108) and RTI-88 has a still better ratio (984 NET/DAT with additionally having less selectivity than the former compound between DAT/SERT and having a more even spread of potency with the ratio between DAT & SERT being 88)
| Compound | DAT
[3H]WIN 35428 |
5-HTT
[3H]Paroxetine |
NET
[3H]Nisoxetine |
Selectivity
5-HTT/DAT |
Selectivity
NET/DAT |
|---|---|---|---|---|---|
| RTI-83 | 55 ± 2.1 | 28.4 ± 3.8 | 4,030 ± 381 | 0.5 | 73.3 |
| RTI-102 | 474 | 1928 | 43,400 | 4.06 | 91.5 |
| RTI-304 | 15 ± 1.2 | 7.1 ± 0.71 | 2,800 ± 300 | 0.5 | 186.6 |
| RTI-88 | 1.35 ± 0.11 | 120 ± 4 | 1,329 ± 124 | 88.9 | 984.0 |
| RTI-143 | 4.06 ± 0.22 | 404 ± 56 | 40,270 ± 180 | 99.5 | 9,919.0 |
Such drugs are speculated to be useful as potential antidepressants, but few examples have been reported in the literature as yet. However while RTI-83 has been used for binding studies to model the monoamine transporter proteins,[3] its pharmacology in vivo has not been studied in detail.
See also
External links
References
- ↑ Blough BE, Abraham P, Lewin AH, Kuhar MJ, Boja JW, Carroll FI. Synthesis and transporter binding properties of 3 beta-(4′-alkyl-, 4′-alkenyl-, and 4′-alkynylphenyl)nortropane-2 beta-carboxylic acid methyl esters: serotonin transporter selective analogs. Journal of Medicinal Chemistry. 1996 Sep 27;39(20):4027-35. PMID 8831768
- ↑ Singh S (March 2000). "Chemistry, design, and structure-activity relationship of cocaine antagonists". Chemical Reviews 100 (3): 925–1024. doi:10.1021/cr9700538. PMID 11749256.
- ↑ Roman DL, Saldaña SN, Nichols DE, Carroll FI, Barker EL. Distinct molecular recognition of psychostimulants by human and Drosophila serotonin transporters. Journal of Pharmacology and Experimental Therapeutics. 2004 Feb;308(2):679-87. PMID 14593087
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