Conformational requirements for endocannabinoid interaction with the cannabinoid receptors, the anandamide transporter and fatty acid amidohydrolase

Anandamide (N-arachidonoylethanolamine) has been identified as an endogenou s ligand of the G-protein coupled cannabinoid CB1 receptor. Recent studies have postulated the existence of carrier-mediated anandamide transport whic h is involved in the termination of the biological effects of anandamide. A membrane bound amidohydrolase (fatty acid amide hydrolase, FAAH), located intracellulary, hydrolyzes and inactivates anandamide and other endogenous cannabinoids such as 2-arachidonoylglycerol (2-AG). Structure-activity rela tionships (SARs) for endocannabinoid interaction with the CB receptors, the anandamide transporter and FAAH are currently emerging in the literature. This review considers the divergences between these SARs and focuses upon t he conformational implications for endocannabinoid recognition at each of t hese biological targets. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.