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)