Metazocine is an

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

analgesic related to pentazocine. While metazocine has significant analgesic effects, mediated through a mixed agonist–antagonist action at the mu opioid receptor, its clinical use is limited by dysphoric and

hallucinogenic Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...

effects which are most likely caused by activity at

kappa opioid receptor Kappa (uppercase Κ, lowercase κ or cursive ; el, κάππα, ''káppa'') is the 10th letter of the Greek alphabet, representing the voiceless velar plosive sound in Ancient and Modern Greek. In the system of Greek numerals, has a value ...

s (where it is a high-efficacy agonist) and/or

sigma receptor Sigma receptors (σ-receptors) are protein cell surface receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, ...

s. 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. 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 prototype

benzomorphan Benzomorphan is a chemical compound that is the base for a series of drugs which variably act on the opioid kappa and sigma receptors, including the following compounds: * 5,9-DEHB * 8-CAC * Alazocine * Anazocine * Bremazocine * Butinazoc ...

, metazocine (6), can be obtained from a variation of the morphinan synthesis. Metazocine synthesis

Thus, reaction of the Grignard reagent from ''p''-methoxybenzyl chloride (1) with the lutidine methiodide (2) affords the benzylated dihydropyridine (3). Reduction of the

enamine An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates. : The word "enamine" is derived from the affix ''en''-, used as the suffix of alkene, and t ...

π-bond leads to the tetrahydropyridine (4). Cyclization by means of acid leads directly to the benzomorphan ring system (5). Demethylation of the aromatic ring system affords the

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...

. Although this last compound is in fact a relatively potent analgesic, it is not available commercially as a drug.

References

{{Opioidergics Benzomorphans Kappa-opioid receptor agonists Phenols Synthetic opioids

Syntheses

See also

References