Endocannabinoid chemical biology: a tool for the development of novel therapies.
The identification of the major psychoactive constituent of Cannabis and marijuana, Delta(9)-tetrahydrocannabinol, opened the way first to the cloning of the G-protein-coupled cannabinoid CB(1) and CB(2) receptors, and then to the isolation and characterisation of their endogenous agonists, the endocannabinoids. Considerable progress has been made in the characterisation of pathways and enzymes for the biosynthesis and degradation of anandamide and 2-arachidonoylglycerol, the two best-known endocannabinoids, as well as of endocannabinoid-related molecules, such as the N-acylethanolamines, which, as in the case of N-palmitoylethanolamine and N-oleoylethanolamine, may interact with other receptor types. However, it is still not fully understood how other plant cannabinoids, of which cannabidiol is the most studied representative, exert their pharmacological effects. Together with these issues, this first review article on the endocannabinoids describes the synthetic pharmacological tools that have been designed so far to interact with the proteins of the 'endocannabinoid system' and that can potentially be used as templates for the development of new therapies.
Petrosino
Stefania
S
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy. spetrosino@icmib.na.cnr.it
Ligresti
Alessia
A
Di Marzo
Vincenzo
V
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery; D063388:Endocannabinoids; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D000099252:Fatty Acid Amide Hydrolases