Ligands of the histamine H3-receptor: new potent antagonists of the 2-thioimidazole type.
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.
Plazzi
P V
PV
Dipartimento Farmaceutico, Università degli Studi di Parma.
Mor
M
M
Bordi
F
F
Silva
C
C
Rivara
S
S
Caretta
A
A
Ballabeni
V
V
Impicciatore
M
M
Vitali
T
T
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
D006633:Histamine Antagonists; D007093:Imidazoles; D008024:Ligands; D018100:Receptors, Histamine H3