Therapeutic potential of endocannabinoid-hydrolysing enzyme inhibitors.
The specific protein target of delta9-tetrahydrocannabinol (delta9-THC), the main active ingredient of Cannabis sativa L., was characterized from rat brain nearly 20 years ago, and several endogenous compounds and proteins comprising the endocannabinoid (eCB) system have since been discovered. It has become evident that the eCB system consists of at least two cannabinoid receptors (i.e. the CB1 and CB2 receptors), in addition to their endogenous ligands (the eCBs) and several enzymes involved in the biosynthesis and catabolism of the eCBs. The two well-established eCBs, N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), are produced by neurons on demand, act near their sites of synthesis and are effectively metabolized by fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL), respectively. Inhibitors specifically targeting these enzymes could offer novel therapeutic approaches (e.g. for the treatment of pain and movement disorders). This MiniReview summarizes the literature concerning the potential therapeutic potential of FAAH and MGL inhibitors.
Saario
Susanna M
SM
Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland. susanna.saario@uku.fi
Laitinen
Jarmo T
JT
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006868:Hydrolysis; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors; D009069:Movement Disorders / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D008994:Monoacylglycerol Lipases; D000099252:Fatty Acid Amide Hydrolases