THE EFFECTS OF PRONETHALOL AND ITS DEXTRO ISOMER UPON EXPERIMENTAL CARDIAC ARRHYTHMIAS

¹ Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan

The beta adrenergic receptor blocking agent, pronethalol, has been shown to produce an antiarrhythmic effect in a variety of experimentally induced cardiac arrhythmias. These observations had led several authors to conclude that the antiarrhythmic action of pronethalol is intimately associated with its ability to produce beta adrenergic receptor blockade.

The availability of the dextro isomer of pronethalol, a compound 40 times less active than the levo isomer in producing beta adrenergic receptor blockade, has permitted an evaluation of the importance of beta adrenergic receptor inhibition in several experimentally induced cardiac arrhythmias.

Cardiac arrhythmias resulting from toxic doses of ouabain or acetylstrophanthidin are readily antagonized by (+)-pronethalol under both in vivo and in vitro conditions. The effectiveness of the dextro isomer was similar to that of dl-pronethalol. Arrhythmias resulting from the combined administration of methylchloroform and epinephrine were also prevented by previous administration of (+)-pronethalol. However, (+)-pronethalol was not effective in preventing ventricular fibrillation resulting from the combined administration of U-0882 and isoproterenol. The latter arrhythmia was prevented by the beta adrenergic receptor blocking agent, dl-pronethalol.

These results demonstrate that beta adrenergic receptor inhibition by pronethalol is not the mechanism through which this compound prevents digitalis or hydrocarbon-epinephrine- induced arrhythmias as has been previously suggested in the literature. That beta adrenergic receptor blockade may be of importance in the prevention of other experimentally induced arrhythmias is suggested by the different actions of (+)-pronethalol and dl-pronethalol against the U-0882-isoproterenol-induced ventricular fibrillation.

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