Cravatt Benjamin F, Lichtman Aron H
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Curr Opin Chem Biol. 2003 Aug;7(4):469-75. doi: 10.1016/s1367-5931(03)00079-6.
The medicinal properties of exogenous cannabinoids have been recognized for centuries and can largely be attributed to the activation in the nervous system of a single G-protein-coupled receptor, CB1. However, the beneficial properties of cannabinoids, which include relief of pain and spasticity, are counterbalanced by adverse effects such as cognitive and motor dysfunction. The recent discoveries of anandamide, a natural lipid ligand for CB1, and an enzyme, fatty acid amide hydrolase (FAAH), that terminates anandamide signaling have inspired pharmacological strategies to augment endogenous cannabinoid ('endocannabinoid') activity with FAAH inhibitors, which might exhibit superior selectivity in their elicited behavioral effects compared with direct CB1 agonists.
外源性大麻素的药用特性已被认可数百年,这在很大程度上可归因于其对单一G蛋白偶联受体CB1在神经系统中的激活作用。然而,大麻素的有益特性,包括缓解疼痛和痉挛,却被认知和运动功能障碍等不良反应所抵消。最近发现了一种CB1的天然脂质配体——花生四烯乙醇胺,以及一种终止花生四烯乙醇胺信号传导的酶——脂肪酸酰胺水解酶(FAAH),这激发了利用FAAH抑制剂增强内源性大麻素(“内源性大麻素”)活性的药理学策略,与直接的CB1激动剂相比,FAAH抑制剂在引发行为效应方面可能表现出更高的选择性。