From cannabis to cannabinergics: new therapeutic opportunities.
The molecular basis of cannabinoid activity is better understood since the discovery of the CB(1) receptor in the mammalian brain and the CB(2) receptor in peripheral tissues. Subsequently, an endogenous CB(1) receptor ligand, arachidonylethanolamide (anandamide), was isolated from porcine brain and shown to be metabolized by the enzyme arachidonylethanolamide amidohydrolase or fatty acid amide hydrolase. Recently, we have characterized a reuptake system for the transport of anandamide across the cell membrane, and have shown that selective inhibition of this transporter is associated with analgesia and peripheral vasodilation. The four cannabinoid system proteins, including the CB(1) and CB(2) receptors, fatty acid amide hydrolase, and the anandamide transporter, are excellent targets for the development of novel medications for various conditions, including pain, immunosuppression, peripheral vascular disease, appetite enhancement or suppression, and motor disorders. During the last decade, numerous selective ligands for each of these proteins were designed and synthesized. Many of these agents serve as important molecular probes, providing structural information about their binding sites, as well as pharmacological tools imparting information about the roles of their targets in physiological and disease states. All of the above compounds that modulate the functions of the endocannabinoid system can be collectively described under the term cannabinergics, regardless of chemical classification or type of resultant pharmacological action.
Serono Reproductive Biology Institute, One Technology Place, Rockland, MA 02370, USA.
Andreas
A
Goutopoulos
Alexandros
A
Makriyannis
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001692:Biological Transport; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002188:Cannabis / Q000737:chemistry*; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006213:Hallucinogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009928:Organ Specificity; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D006213:Hallucinogens; D008024:Ligands; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000581:Amidohydrolases; C087226:arachidonoylethanolamide synthase; C078814:anandamide