Antidysrhythmic actions of meobentine sulfate.
The antiarrhythmic efficacy of meobentine sulfate, a bethanidine derivative lacking inhibitory effects on adrenergic neuronal function, was assessed in three canine models. Intravenous meobentine sulfate, administered in dosages of 5.0, 10,0, and 20.0 mg/kg, produced a dose-related increase in the ventricular fibrillation threshold (VFT) under nonischemic conditions (7.6 +/- 1.8 mA vs 37.8 +/- 8.6 mA) (20 mg/kg; p less than 0.05) and during regional myocardial ischemia (5.6 +/- 1.5 mA vs 41.8 +/- 9.1 mA) (20 mg/kg; p less than 0.05). The VFT was also increased in the presence of chronic ischemic injury (6.4 +/- 1 mA to 31 +/- 10 mA) (20 mg/kg; p 0.05). In the conscious dog, 4 days after an anterior myocardial infarction, programmed electrical stimulation (PES) produced nonsustained ventricular tachycardia (VT) in five dogs. After meobentine sulfate administration, eight of nine animals had sustained VT and one animal developed ventricular fibrillation (VF). At a dose of 20 mg/kg, there was prolongation of the cycle length of the VT (169 +/- 11 msec to 237 +/- 20 msec), prolongation of the QRS duration (58 +/- 2.6 msec to 71 +/- 3.7 msec), and prolongation of the delay in epicardial activation. There was an enhanced potential after meobentine administration for programmed stimulation to produce ventricular arrhythmias with the introduction of fewer premature impulses. In the third canine model, conscious dogs with a previous anterior myocardial infarction developed VF in response to electrically induced left circumflex coronary artery injury. Meobentine (20 mg/kg) failed to prevent VF in eight of eight dogs. These results suggest that while meobentine sulfate significantly increases the electrical VFT, it does not protect the conscious canine from the induction of ventricular tachyarrhythmias in response to PES, and it does not prevent VF in a conscious canine model of sudden coronary death.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003645:Death, Sudden; D004285:Dogs; D004558:Electric Stimulation; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008760:Methylguanidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D013610:Tachycardia / Q000139:chemically induced; D014693:Ventricular Fibrillation / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D008760:Methylguanidine; C032896:meobentine