Also Known As: Mecamylamine, Inversine
Mecamylamine (Inversine) is a nonselective and noncompetitive antagonist of the nicotinic acetylcholine receptors that was introduced in the 1950s as an antihypertensive agent.
Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, it is more often used now as a research tool.
Mecamylamine is also sometimes used as an anti-addictive drug to help people stop smoking tobacco, and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to its blocking α3β4 nicotinic receptors in the brain.
In a recent double-blind, placebo-controlled Phase II trial in Indian patients with major depression, (S)-mecamylamine (TC-5214) appeared to have efficacy as an augmentation therapy. This is the first substantive evidence that shows that compounds where the primary pharmacology is antagonism to neuronal nicotinic receptors will have antidepressant properties. TC-5214 is currently in Phase III of clinical development as an add-on treatment and on stage II as a monotherapy treatment for major depression. The first results reported from the Phase III trials showed that TC-5214 failed to meet the primary goal and the trial did not replicate the effects that had been encouraging in the Phase II trial. Development is funded by Targacept and AstraZeneca. It did not produce meaningful, beneficial results on patients as measured by changes on the Montgomery-Asberg Depression Rating Scale after eight weeks of treatment as compared with placebo.
(S)-(+)-Mecamylamine dissociates more slowly from alpha-4 beta-2 and alpha-3 beta-4 receptors than does the (R)-(-)-enantiomer. The pKa value is 11.2.
A large SAR study of mecamylamine and its analogs was reported by a group from Merck in 1962.Another, more recent SAR study was undertaken by Suchocki et al.