title: Ligands of the histamine H3-receptor: new potent antagonists of the 2-thioimidazole type.
abstract: An overview of H3-receptor ligands is presented, with particular attention to antagonists. The protein binding of the classical H3-receptor antagonist thioperamide and its effect on in vivo distribution are discussed. A series of H3-receptor antagonists characterised by the presence of an imidazole ring, a spacer (ethylthio-, ethylamino-, propylthio- or propylamino-chain), a second heterocycle nucleus and a lipophilic group is described. Their H3-receptor antagonist potency has been measured on electrically stimulated guinea-pig intestine, and their affinity for central H3-receptor has been determined by competitive inhibition of [3H]N alpha-methylhistamine binding to rat cortex. Biphasic inhibition curves have been observed in some cases. Compounds endowed with interesting activity belong mostly to the class of 2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazole, having a phenyl or a cyclohexyl group.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma.
authors.forename: P V
authors.initials: PV
authors.lastname: Plazzi
authors.forename: M
authors.initials: M
authors.lastname: Mor
authors.forename: F
authors.initials: F
authors.lastname: Bordi
authors.forename: C
authors.initials: C
authors.lastname: Silva
authors.forename: S
authors.initials: S
authors.lastname: Rivara
authors.forename: A
authors.initials: A
authors.lastname: Caretta
authors.forename: V
authors.initials: V
authors.lastname: Ballabeni
authors.forename: M
authors.initials: M
authors.lastname: Impicciatore
authors.forename: T
authors.initials: T
authors.lastname: Vitali
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008024:Ligands; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D008024:Ligands; D018100:Receptors, Histamine H3