Nalorphine

Nalorphine

Systematic (IUPAC) name
(5α,6α)-17-allyl- 7,8-didehydro- 4,5-epoxymorphinan- 3,6-diol
Clinical data
AHFS/Drugs.com	International Drug Names
Legal status
Legal status	AU: S4 (Prescription only) CA: Schedule I
Identifiers
CAS Number	62-67-9
ATC code	V03AB02 (WHO)
PubChem	CID 5284595
IUPHAR/BPS	1629
ChemSpider	4447643
UNII	U59WB2WRY2
ChEMBL	CHEMBL415284
Synonyms	(−)−(5R,6S)-9α-allyl- 4,5-epoxymorphin- 7-en- 3,6-diol
Chemical data
Formula	C19H21NO3
Molar mass	311.375 g/mol
SMILES O[C@H]2\C=C/[C@H]5[C@@H]4N(CC[C@@]51c3c(O[C@H]12)c(O)ccc3C4)C\C=C
InChI InChI=1S/C19H21NO3/c1-2-8-20-9-7-19-12-4-6-15(22)18(19)23-17-14(21)5-3-11(16(17)19)10-13(12)20/h2-6,12-13,15,18,21-22H,1,7-10H2/t12-,13+,15-,18-,19-/m0/s1 Key:UIQMVEYFGZJHCZ-SSTWWWIQSA-N
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Nalorphine (INN) (brand names Lethidrone, Nalline), also known as N-allyl-normorphine, is a mixed opioid agonist–antagonist with opioid antagonist and analgesic properties.^[1] It was introduced in 1954^[2] and was used as an antidote to reverse opioid overdose and in a challenge test to determine opioid dependence.^[3] It acts at two opioid receptors — the μ-opioid receptor (MOR) where it has antagonistic effects, and at the κ-opioid receptor (KOR) (K_i = 1.6 nM; EC₅₀ = 483 nM; E_max = 95%) where it exerts high-efficacy partial agonist/near-full agonist characteristics.^[4] Nalorphine was the second opioid antagonist to be introduced, preceded by nalodeine (N-allylnorcodeine) in 1915 and followed by naloxone in 1960 and naltrexone in 1963.^[2] Due to potent activation of the KOR, nalorphine produces side effects such as dysphoria, anxiety, confusion, and hallucinations, and for this reason, is no longer used medically.^[1][2][5]

Synthesis

Nalorphine synthesis:^[6] amended procedure:^[7][8][9]

More recently, it has become much more commonplace to use ethyl chloroformate instead of cyanogen bromide for the Von Braun degradation demethylation step. See for example the list of phenyltropanes or the synthesis of paroxetine for further examples of this.

See also

• Diacetylnalorphine
• Levallorphan
• Nalbuphine
• Nalorphine dinicotinate

References

1. M. Glatt (6 December 2012). The Dependence Phenomenon. Springer Science & Business Media. pp. 121–. ISBN 978-94-011-7457-2.
2. Anil Aggrawal. APC Essentials of Forensic Medicine and Toxicology. Avichal Publishing Company. pp. 554–. ISBN 978-81-7739-441-2.
3. "Medicine: Drug Detector", Time, Dec. 24, 1956
4. Gharagozlou, Parham; Hashemi, Ezzat; DeLorey, TimothyM; Clark, J David; Lameh, Jelveh (2006). "Pharmacological profiles of opioid ligands at Kappa opioid receptors". BMC Pharmacology 6 (1): 3. doi:10.1186/1471-2210-6-3. ISSN 1471-2210.
5. RS Satoskar; Nirmala Rege; SD Bhandarkar (27 July 2015). Pharmacology and Pharmacotherapeutics. Elsevier Health Sciences APAC. pp. 166–. ISBN 978-81-312-4371-8.
6. McCawley et al., J. Am. Chem. Soc. 63, 314 (1941).
7. Weijlard, J.; Erickson, A. E. (1942). "N-Allylnormorphine". Journal of the American Chemical Society 64 (4): 869. doi:10.1021/ja01256a036.
8. Hart, McCawley, J. Pharmacol. 82, 339 (1944)
9. U.S. Patent 2,364,833 (1944); Weijlard, U.S. Patent 2,891,954 (1959 to Merck & Co.).