Comparative cardiovascular effects of three benzimidazole derivatives, AR-L 57 BS, AR-L 100 BS, and AR-L 115 BS.
2-(2,4-Dimethoxyphenyl)-1H-imidazo[4,5-b]-pyridine (AR-L 57 BS), 2-(4-methoxy-2-[(2-methylsulfinyl)ethoxy]-phenyl-3H-imidazo[4,5-b]pyridine (AR-L 100 BS) and 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) increased force of contraction in isolated rat atria at 3-1000 mumol/l by maximally 100%. In anaesthetized cats dp/dtmax was augmented by maximally 141-216% at 0.1-10 mg/kg i.v. Heart rate rose after AR-L 57 BS and AR-L 115 BS by 17-38% and decreased after AR-L 100 BS by 17%. AR-L 57 BS and AR-L 115 BS had weak effects on blood pressure, AR-L 100 BS elevated blood pressure by more than 50%. The effects were rapid in onset and lasted up to 20 min after AR-L 57 BS and AR-L 100 BS and more than 50 min after AR-L 115 BS. Only AR-L 115 BS was orally active. Intravenous toxicity was lowest with AR-L 115 BS and highest with AR-L 100 BS. Oral toxicity was equal for the three compounds. The positive inotropic effects of the benzimidazoles were stronger than that of ouabain and comparable to those of theophylline and isoprenaline.
D000284:Administration, Oral; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D013045:Species Specificity
D002316:Cardiotonic Agents; D007093:Imidazoles; C012633:AR-L 57 CL; C029759:AR-L 100 BS; C029758:sulmazole