Abstrait

The anandamide membrane transporter and the therapeutic implications of its inhibition

Natalia Battista, Valeria Gasperi, Filomena Fezza and Mauro Maccarrone

Endocannabinoids are a new class of lipid mediators that include amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine), the most prominent member of this group together with 2-arachidonoyl glycerol, has several pharmacological actions, even if its life span is quite short because of the presence of an efficient mechanism of cellular removal which involves transport across the plasma membranes and hydrolysis by fatty acid amide hydrolase (FAAH). Here, we review evidence in favor or against the existence of a true anandamide membrane transporter (AMT) and discuss the structural properties of compounds that inhibit AMT without affecting other proteins of the endocannabinoid system, such as cannabinoid receptors or FAAH. Also the therapeutic implications of novel AMT inhibitors will be reviewed in the light of their potential exploitation for the treatment of neurodegenerative diseases and other human pathologies.