Glennon R A, Misenheimer B R
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23289-0581.
Pharmacol Biochem Behav. 1989 Aug;33(4):909-12. doi: 10.1016/0091-3057(89)90491-7.
Tests of stimulus generalization were conducted using rats trained to discriminate 1.5 mg/kg of N-monomethyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane HCl (MDMA) from saline in order to determine if two structurally related analogs (MDE and N-OH MDA) would produce similar stimulus effects. The MDMA-stimulus (MDMA, ED50 value = 0.76 mg/kg) generalized both to MDE (ED50 value = 0.73 mg/kg) and N-OH MDA (ED50 value = 0.47 mg/kg). Administration of (+)amphetamine resulted in partial generalization (maximum of 49% MDMA-appropriate responding) in the MDMA-trained animals. Taken together with our previous studies showing that MDMA substitutes for the phenylisopropylamine stimulant (+)amphetamine, but that neither MDE nor N-OH MDA substitute for (+)amphetamine or for the phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the present results [i.e., MDMA-stimulus generalization to MDE, N-OH MDA, but not to (+)amphetamine] suggest that 1) MDMA produces effects other than those that may be considered amphetamine-like, and 2) MDE and N-OH MDA are MDMA-like agents with even less of an amphetamine-like component of action than MDMA itself.
使用经过训练以区分1.5毫克/千克盐酸N-单甲基-1-(3,4-亚甲二氧基苯基)-2-氨基丙烷(摇头丸)和生理盐水的大鼠进行刺激泛化测试,以确定两种结构相关的类似物(MDE和N-羟基摇头丸)是否会产生相似的刺激效果。摇头丸刺激(摇头丸,ED50值=0.76毫克/千克)既泛化到MDE(ED50值=0.73毫克/千克),也泛化到N-羟基摇头丸(ED50值=0.47毫克/千克)。给予(+)苯丙胺导致在接受摇头丸训练的动物中出现部分泛化(最大49%的摇头丸适宜反应)。结合我们之前的研究表明摇头丸可替代苯异丙胺兴奋剂(+)苯丙胺,但MDE和N-羟基摇头丸都不能替代(+)苯丙胺或苯异丙胺致幻剂1-(2,5-二甲氧基-4-甲基苯基)-2-氨基丙烷(DOM),目前的结果[即摇头丸刺激泛化到MDE、N-羟基摇头丸,但不泛化到(+)苯丙胺]表明:1)摇头丸产生的效果除了那些可能被认为类似苯丙胺的效果之外;2)MDE和N-羟基摇头丸是类似摇头丸的药物,其类似苯丙胺的作用成分比摇头丸本身还要少。