LIGANDS OF THE HISTAMINE H-3 RECEPTOR - NEW POTENT ANTAGONISTS OF THE2-THIOIMIDAZOLE TYPE

An overview on H-3-receptor ligands is presented, with particular atte ntion to antagonists. The protein binding of the classical H-3-recepto r antagonist thioperamide and its effect on in vivo distribution are d iscussed. A series of H-3-receptor antagonists characterised by the pr esence of an imidazole ring, a spacer (ethylthio-, ethylamino-, propyl thio- or propylamino-chain), a second heterocycle nucleus and a lipoph ilic group is described. Their H-3-receptor antagonist potency has bee n measured on electrically stimulated guinea-pig intestine, and their affinity for central H-3-receptor has been determined by competitive i nhibition of [H-3]Na methylhistamine binding to rat cortex. Biphasic i nhibition curves have been observed in some cases. Compounds endowed w ith interesting activity belong mostly to the class of 2-[[2-[4(5)-imi dazolyl]ethyl]thio]imidazole, having a phenyl or a cyclohexyl group.