title: Actions of a newly synthesized compound (711389-S) on various types of experimentally induced arrhythmias in mammalian species in situ.
abstract: We examined effects of 711389-S, a new antiarrhythmic agent, on ouabain-induced arrhythmias in dogs and guinea-pigs, aconitine-induced arrhythmias in dogs and mice, adrenaline-induced arrhythmias in dogs under an anesthetized condition, and arrhythmias induced by coronary artery ligation and occlusion by a glass bead in dogs under conscious and un-restrained conditions. 711389-S (1-3 mg/kg, i.v.) decreased the number of ventricular extrasystoles induced by ouabain in dogs, and the doses of ouabain required to induce various types of arrhythmias were increased by pretreatment of guinea-pigs with intraduodenal application of 711389-S (5-10 mg/kg). In mice, 711389-S (3 mg/kg, i.v. or 10 mg/kg, p.o.) significantly prolonged the time to onset of arrhythmias induced by aconitine infusion. Atrial fibrillation induced by a topical application of aconitine on the atrium was blocked by 711389-S (1 mg/kg, i.v.) in dogs. 711389-S (1-3 mg/kg, i.v.) depressed arrhythmias induced by adrenaline and restored the sinus rhythm by significantly decreasing the number of ventricular ectopic beats induced by coronary ligation or occlusion in dogs. Oral administration of 711389-S (10-30 mg/kg) in dogs markedly depressed the ventricular ectopic beats induced by coronary ligation. The half decay time of 711389-S after a single bolus injection of 711389-S ranged from 60 to 80 min. Results indicate that 711389-S has similar antiarrhythmic effects to those of other Class I antiarrhythmic agents in situ, and they suggest that this compound might have potential usefulness as a new type of antiarrhythmic agent for clinical use.
authors.affiliation: Department of Pharmacology, Kumamoto University Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: N
authors.initials: N
authors.lastname: Hotokebuchi
authors.forename: S
authors.initials: S
authors.lastname: Kimoto
authors.forename: M
authors.initials: M
authors.lastname: Haruna
authors.forename: T
authors.initials: T
authors.lastname: Nakao
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: K
authors.initials: K
authors.lastname: Nishi
mesh_terms: D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010042:Ouabain; D011412:Propanolamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D010042:Ouabain; C044492:711389-S; D004206:Disopyramide; D000157:Aconitine; D004837:Epinephrine