Pavlopoulos Spiro, Thakur Ganesh A, Nikas Spyros P, Makriyannis Alexandros
Department of Pharmaceutical Sciences, University of Connecticut, Storss, CT 06269, USA.
Curr Pharm Des. 2006;12(14):1751-69. doi: 10.2174/138161206776873743.
The cannabinoid receptors CB1 and CB2 are family A, G-protein Coupled Receptors that mediate the effects of cannabinoids, a class of compounds that are so named because the first members were isolates of the cannabis plant. In recent history, there has been much anecdotal evidence that the potent and diverse physiological responses produced by these compounds can be turned to therapeutic benefit for a wide variety of maladies. The remarkable abundance of cannabinoid receptors and the discovery of several endogenous ligands along with enzyme and transporter proteins for which they are substrates, suggests that an endogenous cannabinoid neuromodulatory system is an important mediator of biological function. For these reasons CB1 and CB2 receptors are attractive targets for the design of therapeutic ligands. The action of these receptors, however, may also be modulated by manipulating the enzymes and membrane transporters that regulate the endogenous ligands. Despite the range of physiological processes and activities that are mediated by cannabinoid receptors, it is clear that it is possible to produce ligands that result in differential responses. In this paper, we review the pharmacophoric elements that lead to these differential responses and in order to discuss them in context we present an overview of structural aspects governing cannabinoid receptor function, the cannabinergic system and its physiological functions.
大麻素受体CB1和CB2属于A类G蛋白偶联受体，介导大麻素的作用。大麻素是一类化合物，因其首批成员是从大麻植物中分离出来的而得名。近年来，有许多轶事证据表明，这些化合物产生的强大而多样的生理反应可转化为对多种疾病的治疗益处。大麻素受体的显著丰富以及几种内源性配体的发现，连同它们作为底物的酶和转运蛋白，表明内源性大麻素神经调节系统是生物功能的重要调节因子。出于这些原因，CB1和CB2受体是治疗性配体设计的有吸引力的靶点。然而，这些受体的作用也可能通过操纵调节内源性配体的酶和膜转运蛋白来调节。尽管大麻素受体介导了一系列生理过程和活动，但显然有可能产生导致不同反应的配体。在本文中，我们综述了导致这些不同反应的药效基团元素，为了在背景中讨论它们，我们概述了控制大麻素受体功能、大麻素能系统及其生理功能的结构方面。
