Pranolium chloride (
dimethylpropranolol chloride) is a nonbeta blocking quaternary
ammonium that has structural similarities to
propranolol and
bretylium that exert antiarrhythmic effects in animals. In initial studies, eight patients with chronic ventricular arrhythmias were given gradually increasing intravenous doses of
pranolium (up to 3 mg/kg) obtaining plasma concentrations up to 7 micrograms/ml without change in pulse, blood pressure, or
arrhythmia frequency. We therefore evaluated the response to
pranolium in seven similar patients at doses up to 10 mg/kg as an infusion of 100 microgram/kg/min over 40 to 100 min. At plasma concentrations of 4.7 to 12.2 micrograms/ml, there was suppressing of ventricular ectopic depolarization (greater than 90%) in three subjects and in two others there was partial suppression (49% and 82%).
Arrhythmia frequency was unchanged in two. At plasma concentrations of 4.1 to 17.2 micrograms/ml four subjects developed
nausea (two of these also vomited) and to experienced perioral
numbness. There was no change in sinus heart rate, supine or standing blood pressure, venous reflex response (
adrenergic reflex venoconstriction), or ECG intervals in any subject.
Pranolium appeared to have antiarrhythmic efficacy in five of seven subjects, without evidence of beta-
adrenergic blockade or interference with sympathetic neuron function known to occur with its congeners,
propranolol and
bretylium. There is a narrow margin between
pranolium efficacy and toxicity. It may, however, be a prototype for
antiarrhythmic drugs that do not exert undesirable effects on the
adrenergic nervous system.