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大麻素激动和拮抗活性的药理学评价

Pharmacological evaluation of agonistic and antagonistic activity of cannabinoids.

作者信息

Martin B R, Compton D R, Little P J, Martin T J, Beardsley P M

机构信息

Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0001.

出版信息

NIDA Res Monogr. 1987;79:108-22.

PMID:2830532
Abstract

The behavioral effects of cannabinoids are dependent upon numerous variables which include species differences, dose, experimental conditions, etc. The complexity of the cannabinoid behavioral syndrome certainly complicates attempts to establish biochemical correlates. It is for this reason that attempts are being made to develop analogs that exhibit selective behavioral effects. The pharmacological profile of the analogs that exhibit selective behavioral effects. The pharmacological profile of the analogs summarized in table 6 suggests a tentative classification for the cannabinoids. While there are numerous analogs which produce the entire spectrum of cannabinoid effects, only those discussed within this article are grouped in class 1. CBD and many of its analogs appear to be devoid of cannabinoid effects, but they are capable of producing CNS depression at large doses (class 2). It is our working hypothesis that the compounds in class 2 may be altering membrane peturbation in a nonspecific fashion. This latter effect may or may not be related to the psychoactive cannabinoids. Class 3 compounds are potent CNS depressants that appear to lack other effects that are unique to cannabinoids. These analogs are particularly interesting in that they may be altering membrane function i a specific fashion in contrast to nonspecific effects exerted by analogs in class 2. Analogs in class 4 appear to exert selective CNS depression. While the mechanism by which these analogs are producing their effects may be proven to be different from those postulated, it does appear that a classification of cannabinoid effects is possible through structural alterations in the cannabinoid molecule.

摘要

大麻素的行为效应取决于众多变量,包括物种差异、剂量、实验条件等。大麻素行为综合征的复杂性无疑使建立生化相关性的尝试变得复杂。正是出于这个原因,人们正在努力开发具有选择性行为效应的类似物。具有选择性行为效应的类似物的药理学特征。表6总结的类似物的药理学特征为大麻素提出了一个初步分类。虽然有许多类似物能产生整个大麻素效应谱,但本文中讨论的只有那些被归为第1类。CBD及其许多类似物似乎没有大麻素效应,但它们在大剂量时能够产生中枢神经系统抑制作用(第2类)。我们的工作假设是,第2类中的化合物可能以非特异性方式改变膜扰动。后一种效应可能与精神活性大麻素有关,也可能无关。第3类化合物是强效中枢神经系统抑制剂,似乎缺乏大麻素特有的其他效应。这些类似物特别有趣,因为与第2类类似物产生的非特异性效应相比,它们可能以特定方式改变膜功能。第4类类似物似乎能产生选择性中枢神经系统抑制作用。虽然这些类似物产生效应的机制可能被证明与假设的不同,但通过大麻素分子的结构改变对大麻素效应进行分类似乎是可能的。

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