Peripheral cannabinoid receptor agonists

Hanus L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, Pertwee RG, Ross RA, Mechoulam R, Fride, E. HU-308 a specific agonist for CB2, a peripheral cannabinoid receptor. Proc Natl Acad Sci USA, 1999 25 14228-14233. 

Fride, E., Breuer, A., Hanus, L., Tchilibon, S., Horowitz, M., Mechoulam, R., Garzon, A. (Yissum Research Development Company of the Hebrew University), Agonist specific for the peripheral cannabinoid receptor, WO 0132169. 

Cannabinoid receptors include the CB1 receptors (which have a high incidence in the CNS and inhibit adenylyl cyclase, close Ca2+ channels and open K+ channels via Gai) and CB2 receptors (which are present in immune cells and act via Gai proteins to inhibit adenylyl cyclase). CB1 and CB2 receptors bind the endogenous ligand anandamide (arachi-donylethanolamide) as well as A9-tetrahydroc.annabinol from marijuana (Cannabis saliva). A9-Tetrahydroc,annabinol antagonizes the peripheral CB2 receptor but acts as an agonist for the CNS CB1 receptor. Cannabinoid receptor agonists have appetite stimulant and psychoactive effects and have therapeutic potential for relief from nausea and pain. 

Portier M, Rinaldi-Carmona M, Pecceu F, Combes T, Poinot-Chazel C, Calandra B, Barth F, Le Fur G, Casellas P (1999) SR 144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist. J Pharmacol Exp Ther 288 582-589... 

Bouaboula M, Desnoyer N, Carayon P, Combes T, CaseUas P (1999a) Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2 impUcation for intraceUular signalization cross-regulation. Mol Pharmacol 55 473-480... 

Bouaboula M, Dussossoy D, CaseUas P (1999b) Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528. Implications for receptor biological responses. J Biol Chem 274 20397-20405... 

Felder CC, Nielsen A, Briley EM, Palkovits M, Priller J, Axelrod J, Nguyen DN, Richardson JM, Riggin RM, Koppel GA, Paul SM, Becker GW (1996) Isolation and measurement of the endogenous cannabinoid receptor agonist, anandamide, in brain and peripheral tissues of human and rat. FEBS Lett 393 231-235... 

However A9-tetrahydrocannabinol anatagonizes the peripheral CB2 receptor while acting as an agonist for the CNS CB1 receptor [133]. Cannabinoid receptors mediate the appetite stimulant and psychoactive effects of cannabinoids which have therapeutic potential for relief from nausea and pain [132]. 

Hwang JH, Yaksh TL (1997) The effect of spinal GABA receptor agonists on tactile aUodynia in a surgically-induced neuropathic pain model in the rat. Pain 70 15-22 Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP Jr (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sd U S A 102 3093-3098... 

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