Ross Ruth A
Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Trends Pharmacol Sci. 2007 Nov;28(11):567-72. doi: 10.1016/j.tips.2007.10.006.
In 2005, the first evidence was obtained that the cannabinoid CB(1) receptor contains an allosteric binding site. The site can be recognized by synthetic small molecules, which display a markedly divergent effect on orthosteric ligand affinity versus efficacy; these small molecules are allosteric enhancers of agonist binding affinity and allosteric inhibitors of agonist signalling efficacy. Allosteric modulation heralds a new approach to the manipulation of the endocannabinoid system for therapeutic benefit; it promises to augment the existing portfolio of selective direct agonists, competitive antagonists and enzyme inhibitors.
2005年，首次获得证据表明大麻素CB(1)受体含有一个变构结合位点。该位点可被合成小分子识别，这些小分子对正构配体亲和力与效能显示出明显不同的影响；这些小分子是激动剂结合亲和力的变构增强剂和激动剂信号传导效能的变构抑制剂。变构调节预示着一种操纵内源性大麻素系统以获得治疗益处的新方法；它有望扩充现有的选择性直接激动剂、竞争性拮抗剂和酶抑制剂产品组合。
