Department of Molecular Physiology, Leiden University, 2333 CC Leiden, The Netherlands; email:
Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:441-463. doi: 10.1146/annurev-pharmtox-030220-112741. Epub 2020 Aug 31.
Inspired by the medicinal properties of the plant and its principal component (-)--Δ-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.
受该植物及其主要成分（-）--Δ-四氢大麻酚（THC）药用特性的启发，研究人员开发了多种化合物来调节人体内的内源性大麻素系统。脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MAGL）的抑制剂分别负责内源性大麻素大麻素和 2-花生四烯酰甘油的失活，它们可能具有治疗作用而不会引起与 THC 直接刺激大麻素 CB 受体相关的不良反应。在这里，我们回顾了已进入临床试验的 FAAH 和 MAGL 抑制剂，讨论了潜在的注意事项，并对该领域的发展方向进行了展望。
