METHCATHINONE - A NEW AND POTENT AMPHETAMINE-LIKE AGENT
METHCATHINONE - A NEW AND POTENT AMPHETAMINE-LIKE AGENT
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DOI：
10.1016/0091-3057(87)90164-x
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发表时间：
1987-03-01
影响因子：
3.6
通讯作者：
KALIX, P
中科院分区：
文献类型：
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作者：
GLENNON, RA;YOUSIF, M;KALIX, P
本研究的目的是考察苯异丙胺衍生物的N-单甲基化对苯丙胺类活性的影响。在用被训练来区分1.0 mg/kg(+)-苯丙胺和生理盐水的大鼠的刺激泛化测试中，1-(X-苯基)-2-氨基丙烷的N-单甲基衍生物，其中X=2，4-二甲氧基(2，4-DMA)，3，4-二甲氧基(3，4-DMA)，2，4，5-三甲氧基(2，4，5-TMA)和2-甲氧基-4，5-亚甲基二氧基(MMDA-2)，在评估的剂量下没有产生与苯丙胺相适应的反应。然而，卡西酮的N-单甲基衍生物(即美卡西酮)，与卡西酮一样，导致刺激泛化。使用该试剂的进一步研究表明：(A)在苯丙胺训练的动物中，美卡西酮(ED50=0.37 mg/kg)比外消旋卡西酮或外消旋苯丙胺(ED50=0.71 mg/kg)更有效，(B)美卡西酮能够诱导[~3H]多巴胺预先标记的大鼠尾状核组织释放放射性，其方式与卡西尼酮、苯丙胺和甲基苯丙胺相似，以及(C)美卡西酮对小鼠自发活动的影响比卡西尼酮更强。本研究的结果为典型的精神刺激剂苯丙胺/甲基苯丙胺和卡西酮/美卡西酮之间的结构类比提供了证据，并进一步支持了苯丙胺和卡西酮在药理作用上相对应的概念。
The purpose of the present investigation was to examine the effect of N-monomethylation of phenylisopropylamine derivatives on amphetamine-like activity. In tests of stimulus generalization using rats trained to discriminate 1.0 mg/kg of (+)-amphetamine from saline, the N-monomethyl derivatives of 1-(X-phenyl)-2-aminopropane, where X = 2,4-dimethoxy (2,4-DMA), 3,4-dimethoxy (3,4-DMA), 2,4,5-trimethoxy (2,4,5-TMA), and 2-methoxy-4,5-methylenedioxy (MMDA-2), did not produce amphetamine-appropriate responding at the doses evaluated. However, the N-monomethyl derivative of cathinone (i.e., methcathinone), like cathinone, resulted in stimulus generalization. Further studies with this agent revealed that (a) in the amphetamine-trained animals, methcathinone (ED50 = 0.37 mg/kg) is more potent than racemic cathinone or racemic amphetamine (ED50 = 0.71 mg/kg in both cases), (b) methcathinone is capable of inducing release of radioactivity from [3H]dopamine-prelabeled tissue of rat caudate nucleus in a manner similar to that observed with cathinone, amphetamine, and methamphetamine, and (c) methcathinone is more potent than cathinone as a locomotor stimulant in mice as determined by their effect on spontaneous activity. The results of the present study provide evidence for a structural analogy between the prototypic psychostimulants amphetamine/methamphetamine and cathinone/methcathinone, and lend further support to the concept that amphetamine and cathinone correspond in their pharmacological effects.