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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cannabinergic ligands.

The understanding of the pharmacology surrounding the cannabinergic system has seen many advances since the discovery of the CB1 receptor in the mammalian brain and the CB2 receptor in the periphery. Among these advances is the discovery of the endogenous ligands arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol amide (2-AG), which are selective agonists for the CB1 and CB2 receptors, respectively. These endogenous neuromodulators involved in the cannabinergic system are thought to be produced on demand and are metabolized by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase ( MAG lipase). Recently, we characterized a reuptake system that facilitates the transport of anandamide across the cell membrane and subsequently developed selective inhibitors of this transport, which have been found to have therapeutic potential as analgesic and peripheral vasodilators. The cannabinergic proteins currently being explored, which include the CB1 and CB2 receptors, FAAH and the anandamide transporter, are excellent targets for the development of therapeutically useful drugs for a range of conditions including pain, loss of appetite, immunosuppression, peripheral vascular disease and motor disorders. As cannabinoid research has progressed, various potent and selective cannabimimetic ligands, targeting these four cannabinoid proteins, have been designed and synthesized. Many of these ligands serve as important molecular probes, providing structural information regarding the binding sites of the cannabinergic proteins, as well as pharmacological tools, which have been playing pivotal roles in research aimed at understanding the biochemical and physiological aspects of the endocannabinoid system. This review will focus on some of the current cannabinergic ligands and probes and their pharmacological and therapeutic potential.[1]


  1. Cannabinergic ligands. Palmer, S.L., Thakur, G.A., Makriyannis, A. Chem. Phys. Lipids (2002) [Pubmed]
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