Alazocine

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. 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. Alazocine is described as a potent analgesic, psychotomimetic or hallucinogen, and opioid antagonist. Moreover, one of its enantiomers was the first compound that was found to selectively label the σ1 receptor, and led to the discovery and characterization of the receptor. Alazocine has been encountered as a novel designer drug.

Pharmacology

Pharmacodynamics

Alazocine shows stereoselectivity in its pharmacodynamics. The (−)-enantiomer is a non-selective and high-affinity ligand of the μ-, κ-, and δ-opioid receptors (Ki = 3.0, 4.7, and 15 nM in guinea pig brain membranes) with very low affinity for the sigma σ1 receptor (Ki = 1,800–4,657 nM in guinea pig brain membranes). It acts as a moderate-efficacy partial agonist of the κ-opioid receptor (Ki = 0.4 nM, EC50 = 24 nM, and Emax = 66% for (±)-alazocine against the mouse receptor transfected in HEK293 cells) and as an antagonist of the μ-opioid receptor (Ki = 1.15 nM for (±)-alazocine against the mouse receptor transfected in HEK293 cells). It is also an agonist of the δ-opioid receptor with far lower potency (Ki = not reported, IC50 = 184 nM, and Imax = 68% for (±)-alazocine against the mouse receptor transfected in HEK293 cells).

Conversely, the (+)-stereoisomer has little affinity for the opioid receptors (Ki for 1,900 nM, 1,600 nM, and 19,000 nM for the μ-, κ-, δ-opioid receptors in guinea pig brain membranes) and instead is a selective and high-affinity agonist of the σ1 receptor (Ki = 48–66 nM in guinea pig brain membranes).