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COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors.
European Journal of Pharmacology 2004 July 9
The pharmacology of 3-(2-ethylmorpholino)-5,5'-di(p-bromophenyl)-imidazolidinedione (DML20), 3-(1-hydroxypropyl)-5,5'-di(p-bromophenyl)-imidazolidinedione (DML21) and 3-heptyl-5,5'-di(p-bromophenyl)-imidazolidinedione (DML23) was extended by studying affinity and GTP binding modulation on cannabinoid receptor subtypes (CB1 and CB2) from rat tissues and human cannabinoid receptors expressed in Chinese Hamster Ovary cells. Competitive binding studies indicated that DML20, DML21 and DML23 are selective ligands for cannabinoid CB1 receptors. In rat cerebellum homogenates, DML20, DML21 and DML23 were unable to influence [35S]GTPgammaS binding but competitively inhibit HU 210-induced [35S]GTPgammaS binding (pKB of 6.11 +/- 0.14, 6.25 +/- 0.06 and 5.74 +/- 0.09, respectively), indicating that they act as cannabinoid CB1 receptor neutral antagonists. However, in CHO cells homogenates expressing selectively either human cannabinoid CB1 or CB2 receptors, they behaved as inverse agonists decreasing the [35S]GTPgammaS binding, with similar efficacy. In conclusion, these derivatives exhibit different activities (neutral antagonism and inverse agonism) in the different models of cannabinoid receptors studied.
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