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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Stimulus properties of PMMA: effect of optical isomers and conformational restriction.
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Stimulus properties of PMMA: effect of optical isomers and conformational restriction.

机译：PMMA的刺激特性：光学异构体的作用和构象限制。

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摘要

para-Methoxymethamphetamine (PMMA), a structural hybrid of two central stimulants, lacks stimulant properties but behaves in a manner similar to that of MDMA [N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane]. PMMA has been established as a training drug in drug discrimination studies, and in the present investigation we sought to determine which optical isomer of PMMA is primarily responsible for its stimulus effects. Because PMMA is a conformationally flexible molecule, it was also of interest to determine what conformation is most important for its actions. Accordingly, we prepared and examined S(+)PMMA, R(-)PMMA, and conformationally restricted forms of PMMA: PMMA-AT, TIQ-1, and TIQ-2. S(+)PMMA (ED50 = 0.32 mg/kg) was found to be at least as potent as PMMA (ED50 = 0.41 mg/kg), whereas R(-)PMMA failed to result in complete stimulus generalization. An aminotetralin-like conformation, as found in PMMA-AT (ED50 = 0.29 mg/kg), seems to better account for the actions of PMMA than a tetrahydroisoquinoline-like conformation because TIQ-1 and TIQ-2 failed to result in stimulus generalization. The results of the present study further support the concept that PMMA and MDMA share considerable similarity with respect to their stimulus properties in animals except that PMMA lacks the amphetaminergic stimulant component of action associated with MDMA.
机译：对甲氧基甲基苯丙胺（PMMA）是两种主要兴奋剂的结构混合物，缺乏兴奋剂特性，但其行为类似于MDMA [N-甲基-1-（3,4-亚甲基二氧苯基）-2-氨基丙烷]。 PMMA已被确立为药物歧视研究中的一种训练药物，在本研究中，我们试图确定PMMA的哪种旋光异构体对其刺激作用起主要作用。由于PMMA是一种构象柔性分子，因此确定哪种构象对其作用最重要也引起了人们的兴趣。因此，我们准备并检查了S（+）PMMA，R（-）PMMA和PMMA的构象受限形式：PMMA-AT，TIQ-1和TIQ-2。发现S（+）PMMA（ED50 = 0.32 mg / kg）至少与PMMA（ED50 = 0.41 mg / kg）一样有效，而R（-）PMMA无法导致完全的刺激泛化。在PMMA-AT（ED50 = 0.29 mg / kg）中发现的类似氨基四氢萘的构象似乎比四氢异喹啉样的构象更好地说明了PMMA的作用，因为TIQ-1和TIQ-2未能导致刺激泛化。本研究的结果进一步支持了以下观点：PMMA和MDMA在动物的刺激特性方面具有相当的相似性，只是PMMA缺乏与MDMA相关的苯丙胺能刺激成分。

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