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SEARCHING FOR NOVEL LIGANDS FOR THE CANNABINOID AND RELATED RECEPTORS Pritesh Prakash Kumar September 14,2011 A cell-based, Homogenous Time Resolved Fluorescence (HTRF) method was optimized and used to test a library of 60 putative endocannabinoids for activity towards CB1 or CB2, and to test cannabinoid ligands and fatty acid amides for GPRl19 by measuring cAMP levels in this study. The Z' factors for the assay were greater than 0.5 for all three receptors and the assay was able to can tolerate up to 1 % DMSO demonstrating a robust and suitable technology for screening. The known cannabinoid and GPRl19 agonists exhibited the rank order of potency expected for CB1/CB2/GPRl19. Our data demonstrate that none of the amides, N-acyl amino acids (glycine and alanine) Acyl-dopamines, and Acyl-GABAs was able to activate either CB1 or CB2. However the ethanoamides Dihomo-gamma-linolenoyl ethanolamide (DLEA) and DTEA Docosatetra-7Z,1 OZ, 13Z, 16Z-enoyl ethanolamide (DTEA) were found to activate CB 1 and CB2. Our data provide direct evidence to support the hypothesis that unsaturation in the acyl chain of fatty acid ethanolamides affects the ability of these

Searching for novel ligands for the cannabinoid and related receptors.