title: Comparison of cardiovascular effects of a new calcium channel blocker AH-1058 with those of verapamil assessed in blood-perfused canine heart preparations.
abstract: The cardiovascular effects of AH-1058, a novel calcium channel blocker, were examined in comparison with those of verapamil using canine isolated, blood-perfused papillary muscle, atrioventricular node, and sinoatrial node preparations. Intravenous administration of AH-1058 (20, 50, and 100 microg/kg) or verapamil (20, 50, and 100 microg/kg) to the blood-donor dog induced negative inotropic, dromotropic, and chronotropic effects and a coronary vasodilator action in cross-circulated isolated heart preparations, simultaneously inducing the same cardiac effects in the blood-donor dog. The order of potency of the effects of AH-1058 was ventricular contraction > coronary blood flow >> atrioventricular conduction > sinoatrial automaticity, whereas that of verapamil was coronary blood flow >> atrioventricular conduction >> sinoatrial automaticity > ventricular contraction. The cardiosuppressive effects of AH-1058, especially on ventricular contraction, were slower in onset and longer lasting than those of verapamil. These results suggest that this unique cardiovascular profile of AH-1058 may become beneficial for the treatment of certain pathologic processes, in which selective inhibition of ventricular calcium channels would be essential for drug therapy.
authors.affiliation: Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Takahara
authors.forename: A
authors.initials: A
authors.lastname: Sugiyama
authors.forename: H
authors.initials: H
authors.lastname: Dohmoto
authors.forename: R
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D001643:Bridged Bicyclo Compounds; D002121:Calcium Channel Blockers; D010880:Piperidines; D014700:Verapamil; C119283:AH 1058