title: Synthesis and positive inotropic effects of 1-acyl-5,6-diethoxy-2-methylthiobenzimidazoles.
abstract: A series of 1-acyl-5,6-diethoxy-2-methylthiobenzimidazoles was synthesized and evaluated for inotropic activity. The compounds caused a concentration-dependent positive inotropic effect in isolated guinea-pig papillary muscles. According to the estimated ED50 value, the efficacy of methyl (1) and isonicotinoyl derivatives (6) was similar to that of milrinone. Carbachol markedly reduced the increase of contraction force of compounds 1, 2, 5 and 9. The inotropic effect of compounds 6 and 9 does not seem to be mediated by the direct stimulation of beta-adrenergic receptors. At that time the beta-agonistic properties of the compounds 1 and 2 might be partially involved in the positive inotropic action of these agents. All tested derivatives, as well as milrinone, increased the amplitude of the late component P2 of the biphasic contraction in guinea-pig papillary muscles. These results indicate that benzimidazole derivatives exert their inotropic effect by increasing Ca influx via slow calcium channel into myocardial cells.
authors.affiliation: Institute of Cardiology, Kaunas Medical University, Lithuania.
authors.forename: V
authors.initials: V
authors.lastname: Garaliené
authors.forename: L
authors.initials: L
authors.lastname: Labanauskas
authors.forename: A
authors.initials: A
authors.lastname: Brukstus
authors.forename: V
authors.initials: V
authors.lastname: Dauksas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010277:Parasympathomimetics / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013055:Spectrophotometry, Infrared
chemical_list: D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D002316:Cardiotonic Agents; D007093:Imidazoles; D010277:Parasympathomimetics; D002217:Carbachol; D011433:Propranolol; D020105:Milrinone