Further evidence for an amphetamine-like mechanism of action of the alkaloid cathinone

Abstract

The alkaloid (-)cathinone is a potent stimulant with pharmacological properties closely resembling those of (+)amphetamine. Since (-)cathinone is capable of inducing release at physiological catecholamine storage sites, it has been suggested that (-)cathinone and (+)amphetamine have the same mechanism of action. In the present study, the potency of (-)cathinone in inducing the release of radioactivity from 3H-dopamine prelabelled tissue of the rat caudate nucleus was compared to that of several structural analogs, i.e. to that of four other aminophenones. (-)Cathinone was found to be the most potent of the compounds under investigation, and among these only demethylcathinone had an effect that was within the same order of magnitude as that of (-)cathinone. Furthermore, (-)cathinone and two of its analogs were evaluated in behavioral experiments with regard to their ability to substitute for (+)amphetamine in rats trained to discriminate between (+)amphetamine and saline. It was found that, unlike the other aminophenones, (-)cathinone is capable of producing (+)amphetamine-like stimulus effects, and these can be antagonized by haloperidol in a dose-related manner. Taken together, these findings support the hypothesis that (+)amphetamine and (-)cathinone produce their central stimulant effect via the same dopaminergic mechanism.