Glennon R A, Young R, Martin B R, Dal Cason T A
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540, USA.
Pharmacol Biochem Behav. 1995 Apr;50(4):601-6. doi: 10.1016/0091-3057(94)00348-3.
With regard to its chemical structure, methcathinone is to cathinone what methamphetamine is to amphetamine. Although it is a drug of abuse outside the United States, methcathione is only recently making an appearance on the clandestine market in this country and has just been classified a Schedule I substance under the Emergency Scheduling Act. We have previously demonstrated that racemic methcathinone produces locomotor stimulation in mice, and substitutes for cocaine and (+)amphetamine in rats trained to discriminate either cocaine or (+)amphetamine, respectively, from saline in tests of stimulus generalization. Because an enantiomeric potency comparison has never been reported for the optical isomers of methcathinone, in the present investigation we synthesized samples of S(-)- and R(+)methcathinone and compared them for their 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-appropriate responding in rats trained to discriminate 1.0 mg/kg of (+)amphetamine from saline vehicle. S(-)Methcathinone was about twice as potent as S(+)amphetamine and three to five times more potent than R(+)methcathinone in the three pharmacologic assays. We conclude that both optical isomers possess central stimulant character, but that S(-)methcathinone is somewhat more potent than R(+)methcathinone.
就其化学结构而言，甲卡西酮与去甲伪麻黄碱的关系就如同甲基苯丙胺与苯丙胺的关系。尽管在美国境外它是一种滥用药物，但甲硫酮最近才在该国的地下市场出现，并且刚刚根据《紧急调度法案》被列为一类管制物质。我们之前已经证明，消旋甲卡西酮在小鼠中会产生运动兴奋作用，并且在分别经过训练以区分可卡因或（+）苯丙胺与生理盐水的大鼠的刺激泛化试验中，它可以替代可卡因和（+）苯丙胺。由于从未有过关于甲卡西酮光学异构体对映体效力比较的报道，在本研究中，我们合成了S（-）-和R（+）-甲卡西酮样品，并比较它们在以下方面的能力：a）在小鼠中产生运动兴奋作用；b）在经过训练以区分8.0mg/kg可卡因与生理盐水载体的大鼠中引发类似可卡因的反应；c）在经过训练以区分1.0mg/kg（+）苯丙胺与生理盐水载体的大鼠中引发（+）-苯丙胺适当的反应。在这三种药理学试验中，S（-）-甲卡西酮的效力约为S（+）-苯丙胺的两倍，比R（+）-甲卡西酮强三到五倍。我们得出结论，两种光学异构体都具有中枢兴奋特性，但S（-）-甲卡西酮比R（+）-甲卡西酮的效力稍强。
