Alazocine
Clinical data | |
---|---|
Other names | SKF-10047; WIN-19631; N-Allylnormetazocine; NANM; NAN; ANMC; 2'-Hydroxy-5,9-dimethyl-2-allyl-6,7-benzomorphan |
ATC code |
|
Identifiers | |
| |
CAS Number |
|
PubChem CID | |
ChemSpider | |
UNII | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.162.264 |
Chemical and physical data | |
Formula | C17H23NO |
Molar mass | 257.377 g·mol−1 |
3D model (JSmol) | |
| |
| |
(what is this?) (verify) |
Alazocine (developmental code name SKF-10047), also known more commonly as N-allylnormetazocine (NANM), is a synthetic opioid analgesic of the benzomorphan family related to metazocine, which was never marketed.[1][2][3] In addition to its opioid activity, the drug is a sigma receptor agonist, and has been used widely in scientific research in studies of this receptor.[4][5] Alazocine is described as a potent analgesic, psychotomimetic or hallucinogen, and opioid antagonist.[2] Moreover, one of its enantiomers was the first compound that was found to selectively label the
Pharmacology
[edit]Pharmacodynamics
[edit]Alazocine shows stereoselectivity in its pharmacodynamics.[6] The (−)-enantiomer is a non-selective and high-affinity ligand of the
Conversely, the (+)-stereoisomer has little affinity for the opioid receptors (Ki for 1,900 nM, 1,600 nM, and 19,000 nM for the
Both enantiomers of alazocine have very low affinity for the sigma
Taken together, (−)-alazocine is a selective partial agonist of the
History
[edit]Alazocine was one of the early members of the benzomorphan family of opioid analgesics to be investigated.[1] It was first described in the scientific literature in 1961.[12] Its development resulted from nalorphine (N-allylnormorphine), a potent analgesic and opioid antagonist with similar pharmacology which had been introduced in the mid-1950s.[1] Alazocine was found to produce strong psychotomimetic effects in humans, and it was not further developed for clinical use.[13][1] Subsequently, other benzomorphans, such as pentazocine (an N-dimethylallylbenzomorphan), cyclazocine (an N-cyclopropylmethylbenzomorphan), and phenazocine (an N-phenylethylbenzomorphan), were developed, and some have been marketed for use as analgesics.[1]
The sigma
References
[edit]- ^ a b c d e Casy AF, Parfitt RT (29 June 2013). Opioid Analgesics: Chemistry and Receptors. Springer Science & Business Media. pp. 176–178, 420–421. ISBN 978-1-4899-0585-7.
- ^ a b Keats AS, Telford J (1964). "Narcotic Antagonists as Analgesics". Molecular Modification in Drug Design. Advances in Chemistry. Vol. 45. pp. 170–176. doi:10.1021/ba-1964-0045.ch014. ISBN 0-8412-0046-7. ISSN 0065-2393.
- ^ Iwamoto ET (February 1981). "Pharmacologic effects of N-allylnormetazocine (SKF-10047)". NIDA Research Monograph. 34: 82–8. PMID 6783955.
- ^ a b Narayanan S, Bhat R, Mesangeau C, Poupaert JH, McCurdy CR (January 2011). "Early development of sigma-receptor ligands". Future Medicinal Chemistry. 3 (1): 79–94. doi:10.4155/fmc.10.279. PMID 21428827.
- ^ a b c d e f g Hayashi T, Su TP (2004). "Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders". CNS Drugs. 18 (5): 269–84. doi:10.2165/00023210-200418050-00001. PMID 15089113. S2CID 72726251.
- ^ a b c d Tam SW (February 1985). "(+)-[3H]SKF 10,047, (+)-[3H]ethylketocyclazocine, mu, kappa, delta and phencyclidine binding sites in guinea pig brain membranes". European Journal of Pharmacology. 109 (1): 33–41. doi:10.1016/0014-2999(85)90536-9. PMID 2986989.
- ^ a b c d e Hellewell SB, Bowen WD (September 1990). "A sigma-like binding site in rat pheochromocytoma (PC12) cells: decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that of guinea pig brain". Brain Research. 527 (2): 244–53. doi:10.1016/0006-8993(90)91143-5. PMID 2174717. S2CID 24546226.
- ^ a b Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J (January 2006). "Pharmacological profiles of opioid ligands at kappa opioid receptors". BMC Pharmacology. 6: 3. doi:10.1186/1471-2210-6-3. PMC 1403760. PMID 16433932.
- ^ a b Gharagozlou P, Demirci H, David Clark J, Lameh J (January 2003). "Activity of opioid ligands in cells expressing cloned mu opioid receptors". BMC Pharmacology. 3: 1. doi:10.1186/1471-2210-3-1. PMC 140036. PMID 12513698.
- ^ a b Gharagozlou P, Demirci H, Clark JD, Lameh J (November 2002). "Activation profiles of opioid ligands in HEK cells expressing delta opioid receptors". BMC Neuroscience. 3: 19. doi:10.1186/1471-2202-3-19. PMC 137588. PMID 12437765.
- ^ a b c d e Chou YC, Liao JF, Chang WY, Lin MF, Chen CF (March 1999). "Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan". Brain Research. 821 (2): 516–9. doi:10.1016/s0006-8993(99)01125-7. PMID 10064839. S2CID 22762264.
- ^ Gordon M, Lafferty JJ, Tedeschi DH, Eddy NB, May EL (December 1961). "A new potent analgetic antagonist". Nature. 192 (4807): 1089. Bibcode:1961Natur.192.1089G. doi:10.1038/1921089a0. PMID 13900480. S2CID 4212447.
- ^ a b c d Almeida O, Shippenberg TS (6 December 2012). Neurobiology of Opioids. Springer Science & Business Media. pp. 356–. ISBN 978-3-642-46660-1.
- ^ a b Schüttler J, Schwilden H (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 97–. ISBN 978-3-540-74806-9.
- ^ Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (June 1976). "The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog". The Journal of Pharmacology and Experimental Therapeutics. 197 (3): 517–32. PMID 945347.