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Abstract：
Methcathinone (MCAT; 1), the progenitor of numerous and widely abused \"synthetic cathinone\" central stimulants, exists as a pair of optical isomers. Although S(-)MCAT is several-fold more potent than R(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (i.e., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats, S(-)MCAT was approximately twice as potent as its R-enantiomer. Achiral analogs, α-methyl MCAT (3) and α-des-methyl MCAT (4), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.
摘要：
甲卡西酮(MCAT;1),大量和广泛滥用的“合成卡西酮”中枢兴奋剂的祖先，作为一对光学异构体存在。尽管S（-）MCAT在啮齿动物运动刺激和大鼠药物辨别测定中的刺激泛化研究中比R（）MCAT有效几倍，MCAT的各个光学异构体从未直接比较过它们对单胺转运蛋白的作用,而单胺转运蛋白似乎是它们作用的基础,也从未检查过它们的相对滥用潜力.这里,我们发现MCAT的异构体在多巴胺和去甲肾上腺素转运蛋白(DAT和NET，分别)作为运输基质(即，作为释放剂），并且在5-羟色胺转运蛋白（SERT）上的效力降低≥63倍。在颅内自我刺激（ICSS）研究中，评估大鼠滥用相关药物的作用，S(-)MCAT的效力大约是其R-对映异构体的两倍。非手性类似物，α-甲基MCAT(3)和α-去甲基MCAT(4)，也是DAT/NET底物，也产生了与滥用有关的ICSS效应，表明它们保留了滥用的潜力，并且它们可能可用于进一步研究具有手性β-（或其他）取代基的合成卡辛酮类似物的立体化学。
