Metazocine is an opioidanalgesic related to pentazocine. While metazocine has significant analgesic effects,[1] mediated through a mixed agonist–antagonist action[2] at the mu opioid receptor,[3] its clinical use is limited by dysphoric and hallucinogenic effects which are most likely caused by activity at kappa opioid receptors (where it is a high-efficacy agonist)[4] and/or sigma receptors.[5][6]
Metazocine is in Schedule II of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN 9240 with a 19 gram aggregate manufacturing quota as of 2014. The free base conversion ratio for salts includes 0.81 for the hydrochloride and 0.74 for the hydrobromide.[7] It is listed under the Single Convention for the Control of Narcotic Substances 1961 and is controlled in most countries in the same fashion as is morphine.
Syntheses[]
The prototypebenzomorphan, metazocine (6), can be obtained from a variation of the morphinansynthesis.
Thus, reaction of the Grignard reagent from p-methoxybenzyl chloride (1) with the lutidine methiodide (2) affords the benzylated dihydropyridine (3). Reduction of the enamineπ-bond leads to the (4). Cyclization by means of acid leads directly to the benzomorphan ring system (5). Demethylation of the aromatic ring system affords the phenol. Although this last compound is in fact a relatively potent analgesic, it is not available commercially as a drug.
See also[]
Phenazocine
Pentazocine
Cyclazocine
Org 6582, a functional MAT inhibitor that is otherwise analogous in structure to the parent compound of article
References[]
^Hori M, Ban M, Imai E, Iwata N, Suzuki Y, Baba Y, Morita T, Fujimura H, Nozaki M, Niwa M (November 1985). "Novel nonnarcotic analgesics with an improved therapeutic ratio. Structure-activity relationships of 8-(methylthio)- and 8-(acylthio)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines". Journal of Medicinal Chemistry. 28 (11): 1656–61. doi:10.1021/jm00149a020. PMID2999399.
^Berzetei-Gurske I, Loew GH (1990). "The novel antagonist profile of (-)metazocine". Progress in Clinical and Biological Research. 328: 33–6. PMID2154788.
^Shannon HE (July 1982). "Pharmacological analysis of the phencyclidine-like discriminative stimulus properties of narcotic derivatives in rats". The Journal of Pharmacology and Experimental Therapeutics. 222 (1): 146–51. PMID7086696.
^Slifer BL, Balster RL, May EL (October 1986). "Reinforcing and phencyclidine-like stimulus properties of enantiomers of metazocine". Pharmacology, Biochemistry, and Behavior. 25 (4): 785–9. doi:10.1016/0091-3057(86)90388-6. PMID3786338. S2CID32126170.
^"Quotas - 2014". Diversion Control Division. U.S. Department of Justice, Drug Enforcement Administration.
^May EL, Fry EM (1957). "Structures Related to Morphine. VIII. Further Syntheses in the Benzomorphan Series*1,2". The Journal of Organic Chemistry. 22 (11): 1366–1369. doi:10.1021/jo01362a017.
^May EL, Ager JH (1959). "Structures Related to Morphine. XI.1Analogs and a Diastereoisomer of 2'-Hydroxy-2,5,9-trimethyl-6,7-benzomorphan". The Journal of Organic Chemistry. 24 (10): 1432–1435. doi:10.1021/jo01092a011.
Salvinorin A Also indirect D2 agonists, such as dopamine reuptake inhibitors (cocaine, methylphenidate), releasing agents (amphetamine, methamphetamine), and precursors (levodopa).