METHCATHINONE (CAT) - AN ENANTIOMERIC POTENCY COMPARISON

With regard to its chemical structure, methcathinone is to cathinone w hat methamphetamine is to amphetamine. Although it is a drug of abuse outside the United States, methcathinone is only recently making an ap pearance on the clandestine market in this country and has just been c lassified a Schedule I substance under the Emergency Scheduling Act. W e have previously demonstrated that racemic methcathinone produces loc omotor stimulation in mice, and substitutes for cocaine and (+)ampheta mine in rats trained to discriminate either cocaine or (+)amphetamine, respectively, from saline in tests of stimulus generalization. Becaus e an enantiomeric potency comparison has never been reported for the o ptical isomers of methcathinone, in the present investigation we synth esized samples of S(-)- and R(+)methcathinone and compared them for th eir ability: a) to produce locomotor stimulation in mice, b) to elicit cocaine-like responding in rats trained to discriminate 8.0 mg/kg of cocaine from saline vehicle, and c) to elicit (+)-amphetamine-appropri ate responding in rats trained to discriminate 1.0 mg/kg of (+)ampheta mine from saline vehicle. S(-)Methcathinone was about twice as potent as S(+)amphetamine and three to five times more potent than R(+)methca thinone in the three pharmacologic assays. We conclude that both optic al isomers possess central stimulant character, but that S(-)methcathi none is somewhat more potent than R(+)methcathinone.