HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

Autor:	Haj CG; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.)., Sumariwalla PF; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.)., Hanuš L; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.)., Kogan NM; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.)., Yektin Z; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.)., Mechoulam R; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.) mechou@cc.huji.ac.il ruthg@ekmd.huji.ac.il., Feldmann M; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.)., Gallily R; Institute for Drug Research (C.G.H., L.H., N.M.K., R.M.) and Lautenberg Center for Immunology (Z.Y., R.G.), Hebrew University Medical Faculty, Jerusalem, Israel; and Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom (P.F.S., M.F.) mechou@cc.huji.ac.il ruthg@ekmd.huji.ac.il.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2015 Oct; Vol. 355 (1), pp. 66-75. Date of Electronic Publication: 2015 Aug 13.
DOI:	10.1124/jpet.115.226100
Abstrakt:	Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu