IN-VITRO CHARACTERIZATION OF POTENCY, AFFINITY AND SELECTIVITY OF H-3ANTAGONISTS - FROM THIOPERAMIDE TO THIOPERAMIDE UNRELATED IMIDAZOLE DERIVATIVES

This paper summarizes the findings obtained for three different series of original compounds designed as potential H-3-antagonists starting from thioperamide structure. The compounds were tested in functional a nd binding assays to estimate their potency, affinity and selectivity for histamine H-3 receptors. Among them, many non-thiourea/isothiourea derivatives acted as selective H-3 competitive antag onists and, part icularly, 4(5)-{2-[4(5)-cyclohexylimidazol-2-ylthio]ethyl} imidazole ( dIII) proved to be the most potent H-3 blocker vs (R)-alpha-methylhist amine in electrically-stimulated ileum. This imidazole derivative, dev oid of thiourea dependent toxic effects, with high affinity displaced biphasically [H-3]-N-alpha-methylhistamine bound to rat brain H-3 site s. Thus, such compound could be proposed as the prototype molecule for the development of new non-thiourea/isothiourea H-3-antagonists and a s experimental tool to explore the intriguing question of H-3 receptor heterogeneity.