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Therapeutic potential of endocannabinoid-hydrolysing enzyme inhibitors.

Basic & clinical pharmacology & toxicology 2007 Nov 1; 101(5):287-93

Link to PubMed abstract

Saario S SM, Laitinen J JT

Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.

The specific protein target of Delta(9)-tetrahydrocannabinol (Delta(9)-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 CB(1) and CB(2 )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.

Keywords: cannabinoids