Assessment of the MDA and MDMA optical isomers in a stimulant-hallucinogen discrimination
Assessment of the MDA and MDMA optical isomers in a stimulant-hallucinogen discrimination
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DOI：
10.1016/s0091-3057(96)00334-6
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发表时间：
1997-08-01
影响因子：
3.6
通讯作者：
Taylor, MM
中科院分区：
文献类型：
--
作者：
Baker, LE;Taylor, MM
苯基异丙胺衍生物3，4-亚甲基二氧基甲基苯丙胺(MDMA)和3，4-亚甲基二氧基苯丙胺(MDA)在药物鉴别调查中与精神刺激剂和致幻剂进行了比较。这些化合物的立体异构体，特别是丙二醛的立体异构体，似乎产生了不同的效果。以前的研究表明，被训练来区分车辆中的苯丙胺的动物泛化成S(+)-异构体，而不是丙二醛和亚甲基四氢叶酸的R(-)异构体，而训练来区分LSD和生理盐水的动物泛化为R(-)-丙二醛，但都不是亚甲基二氧甲基安非他明的异构体。然而，被训练来区分梅斯卡林和载体的动物普遍适用于这些苯基异丙胺衍生物的两种立体异构体。本研究包括两个实验，其中采用三种选择的药物辨别程序来比较丙二醛和MDMA的立体异构体与苯丙胺和美斯卡林(实验一)或LSD(实验二)。对16只雄性SD大鼠进行了辨别S(+)-苯丙胺(1.0 mg/kg)和美斯卡林(12.5 mg/kg)的训练，并训练了8只大鼠在三种选择的食物强化药物辨别程序中区分S(+)-苯丙胺(1.0 mg/kg)和LSD(0.08 mg/kg)。用丙二醛和MDMA的异构体进行替代试验。在第二个实验中，用较低剂量的训练化合物以及兴奋剂可卡因和致幻剂2，5-二甲氧基-4-甲基苯基异丙胺(DOM)进行替代测试。在这两个实验中，所有的异构体对S(+)-苯丙胺杠杆的反应都很少。在第一个实验中，R(-)-丙二醛和R(-)-MDMA几乎完全取代了Mescaline。第二个实验的结果显示，用MDMA和S(+)-丙二醛的两种异构体部分取代了LSD，并用R(-)丙二醛几乎完全取代了LSD。目前的发现不支持先前关于S(+)-亚甲基四氢叶酸和S(+)-丙二醛取代S(+)-苯丙胺的报道。三级药物辨别程序可提供一种更灵敏的行为分析方法，用于检验具有复合刺激特性的药物的辨别刺激效应。(C)1997年爱思唯尔科学公司。
The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants and hallucinogens in drug discrimination investigations. The stereoisomers of these compounds, in particular those of MDA, appear to produce differential effects. Previous studies have demonstrated that animals trained to discriminate amphetamine from vehicle generalize to the S(+)-isomers but not the R(-)-isomers of MDA and MDMA while animals trained to discriminate LSD from saline generalize to R(-)-MDA and neither isomer of MDMA. However, animals trained to discriminate mescaline from vehicle generalize to both stereoisomers of these phenylisopropylamine derivatives. The present study consisted of two experiments in which a three-choice drug discrimination procedure was employed to compare the stereoisomers of MDA and MDMA to both amphetamine and either mescaline (experiment one) or LSD (experiment two). Sixteen male Sprague-Dawley rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and mescaline (12.5 mg/kg) and eight rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and LSD (0.08 mg/kg) from saline in three-choice, food reinforced drug discrimination procedures. Substitution tests were administered with the isomers of MDA and MDMA. In the second experiment, substitution tests were also administered with lower doses of each training compound and with the stimulant cocaine and the hallucinogen 2,5-dimethoxy-4-methylphenylisopropylamine (DOM). In both experiments, all of the isomers produced very few responses on the S(+)-amphetamine lever. In the first experiment, R(-)-MDA and R(-)-MDMA produced nearly complete substitution for mescaline. The results of the second experiment revealed partial substitution for LSD with both isomers of MDMA and S(+)-MDA, and nearly complete substitution with R(-)MDA for LSD. The present findings do not support previous reports that S(+)-MDMA and S(+)-MDA substitute for S(+)-amphetamine. The three-lever drug discrimination procedure may provide a more sensitive behavioral assay in which to examine the discriminative stimulus effects of drugs with compound stimulus properties. (C) 1997 Elsevier Science Inc.