ENDOGENOUS LIGANDS--ROLE IN NEUROLOGICAL DISORDERS

$155,901P01FY2000DANIH

Virginia Commonwealth University, Richmond VA

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Abstract

Anandamide and 2-arachidonoyl-glycerol (2-Ara-Gl) which we isolated from porcine brain in 1992 and from canine gut in 1995 respective are the major endogenous cannabinoids identified so far. Anandamide is accompanied by numerous acylethanolamides; 2-Ara-Gl is accompanies by numerous 2-acyl- glycerols. We have preliminary data which indicates that these entourage compounds" enhance receptor binding of the endogenous ligands, potentiate their in vivo effects and inhibit their hydrolysis. We plan to explore these preliminary findings. We also plan to investigate whether anandamide and/or 2-Aa-Gl have cerebroprotective effects. Preliminary data with anandamide point in this direction. We have synthesized arachidonoyl derivatives which are non hydrolysable. We plan to investigate their properties and compare them to 2-Ara-Gl and anandamide. Finally, we plan to synthesize the major cannabidiol metabolites, 7-hydroxyl-cannabidiol and cannabidiol-7-oic acid and test their possible interactions with THC binding and on in vivo activity.

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