Discriminative stimulus effects of S(-)-methcathinone (CAT):: a potent stimulant drug of abuse

Methcathinone ("CAT") is a CNS stimulant that is a very significant drug of abuse in the former Soviet Union. It has also appeared on the clandestine market in the United States and has been recently classified as a Schedule I substance. In the present study, S(-)-methcathinone [S(-)-CAT, 0.50 mg/kg, IF] was employed as the training drug in a two-lever drug discrimination task in rats. Once established, the S(-)-CAT stimulus was shown to have a rapid onset to action (within 5 min) and a duration of effect of approximately 60-90 min. In tests of stimulus generalization (substitution), the S(-)-CAT (ED50 = 0.11 mg/kg) stimulus generalized to S(-)-methamphetamine (ED50 = 0.17 mg/kg), S(-)-cathinone (ED50 = 0.19 mg/kg), S(+)-amphetamine (ED50 = 0.23 mg/kg), aminorex (ED50 = 0.27 mg/kg), (+/-)-CAT (ED50 = 0.25 mg/kg), (+)-cathinone (ED50 = 0.41 mg/kg), R(+)-CAT (ED50 = 0.43 mg/kg), cis-4-methylaminorex (ED50 = 0.49 mg/kg), methylphenidate (ED50 = 0.83 mg/kg), and cocaine (ED50 = 1.47 mg/kg). S(-)CAT-stimulus generalization did not occur to fenfluramine, a structurally related nonstimulant anorectic. Lastly, haloperidol (AD(50) = 0.18 mg/kg), a dopamine receptor antagonist, potently antagonized the S(-)CAT stimulus. It is concluded that S(-)-methcathinone is a very potent CNS stimulant, which appears to produce its stimulus effect, at least in part, via a dopaminergic mechanism.