title: Discriminative stimulus effects of S(-)-methcathinone (CAT): a potent stimulant drug of abuse.
abstract: 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, IP] 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 (ED5 = 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 (AD50 = 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond 23298-0540, USA.
authors.forename: R
authors.initials: R
authors.lastname: Young
authors.forename: R A
authors.initials: RA
authors.lastname: Glennon
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000697:Central Nervous System Stimulants; D011427:Propiophenones; D005277:Fenfluramine; C047806:monomethylpropion; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol