Cocaine-like discriminative stimulus effects of amphetamine, cathinone, methamphetamine, and their 3,4-methylenedioxy analogs in male rhesus monkeys

Smith, D. A., Blough, B. E., & Banks, M. L. (2017). Cocaine-like discriminative stimulus effects of amphetamine, cathinone, methamphetamine, and their 3,4-methylenedioxy analogs in male rhesus monkeys. Psychopharmacology, 234(1), 117-127. DOI: 10.1007/s00213-016-4444-1

Rationale Synthetic cathinones have emerged as the newest class of abused monoamine transporter substrates. Structurally, these compounds are all beta-ketone amphetamine (cathinone) analogs. Whether synthetic cathinone analogs produce differential behavioral effects from their amphetamine analog counterparts has not been systematically examined. Preclinical drug discrimination procedures have been useful for determining the structure activity relationships (SARs) of abused drugs; however, direct comparisons between amphetamine and cathinone analogs are lacking and, in particular, in non-human primate models.

The study aim was to determine the potency and time course of (+/-)-amphetamine, (+/-)-cathinone, and (+/-)-methamphetamine and their 3,4-methylenedioxy analogs (+/-)-MDA, (+/-)-MDC, and (+/-)-MDMA, respectively, to produce cocaine-like discriminative stimulus effects. If cathinone analogs have similar behavioral pharmacological properties to their amphetamine counterparts, then we would predict similar potencies and efficacies to produce cocaine-like discriminative stimulus effects.

Male rhesus monkeys (n = 4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure.

Racemic amphetamine, cathinone, and methamphetamine produced dose-dependent and full substitution, >= 90 % cocaine-appropriate responding, in all monkeys. Addition of 3,4-methylenedioxy moiety attenuated both the potency and efficacy of amphetamine (MDA), cathinone (MDC), and methamphetamine (MDMA) to produce full cocaine-like effects. Moreover, the cocaine-like effects of amphetamine and cathinone were attenuated to a greater extent than those of methamphetamine or previously published methcathinone (Smith et al. 2016).

The presence of an N-methyl group blunted both the potency and the efficacy shift of the 3,4-methylenedioxy addition for both amphetamine and cathinone analogs.