Cardiac electrophysiologic actions of KB-944 (Fostedil), a new calcium antagonist, in the anesthetized dog.
The cardiac electrophysiologic actions of a novel calcium antagonist, KB-944 [Fostedil, Abbott-53986, diethyl 4-(benzothiazol-2-yl) benzylphosphonate], were examined in anesthetized dogs. Cumulative doses of 0.5, 2.5 and 12.5 mg/kg i.v. produced dose-dependent increases in atrioventricular (AV) nodal refractoriness and conduction time (AH interval), although failing to alter atrial or ventricular refractoriness. Intra-atrial, infranodal and intraventricular conduction (PA, HV and H-EG intervals, respectively) were unchanged. In three of nine dogs, 2.5 to 12.5 mg/kg of KB-944 produced third degree AV blockade. Pretreatment with propranolol (0.1 mg/kg) was accompanied by sinoatrial blockade in three of five dogs who later received 12.5 mg/kg of KB-944. Glucagon (4 micrograms/kg) reversed the electrophysiologic changes associated with administration of KB-944 alone or in conjunction with propranolol. An examination of the temporal profiles of the cardiac electrophysiologic effects of KB-944 indicated selective alterations in AV nodal conduction and refractoriness for durations of approximately 60, 120 and 180 to 240 min after administration of 0.3, 1.0 or 3.0 mg/kg i.v. These results suggest that KB-944 may be an effective agent for treatment of supraventricular tachyarrhythmias via selective depression of the AV nodal conduction system.
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D052160:Benzothiazoles; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004562:Electrocardiography; D004594:Electrophysiology; D005934:Glucagon / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
D052160:Benzothiazoles; D013844:Thiazoles; D005934:Glucagon; D011433:Propranolol; C035950:fosfedil