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The action of reserpine, 6-hydroxydopamine, and bretylium on digitalis-induced cardiotoxicity
Journal article   Peer reviewed

The action of reserpine, 6-hydroxydopamine, and bretylium on digitalis-induced cardiotoxicity

Claire M. Lathers, Judy L. Gerard.Ciminera, Steven I. Baskin, John C. Krusz, Gerald J. Kelliher, Jay Roberts and James R Roberts
European journal of pharmacology, v 76(4), pp 371-379
1981
DOI: https://doi.org/10.1016/0014-2999(81)90108-4
PMID: 6799304
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

6-Hydroxydopamine Adrenergic nerve terminal Arrhythmia Bretylium Cardiac glycosides Digitalis Ouabain Reserpine
This study determined whether the protective effect of reserpine against ouabain-induced ventricular arrhythmias in the cat is due to an action of the drug on the adrenergic nerve terminal. Rescrpine (5 mg/kg i.p.) administered 24 h prior to ouabain (2 μg/kg per min i.v., until death) increased the dose of ouabain to produce premature ventricular contractions, ventricular tachycardia, and death from 77.3 ± 5.2 to 105.0 ± 6.0; 84.9 ± 5.2 to 132.7 ± 9.1; and 108.8 ± 4.0 to 165.7 ± 10.4 μg/kg, respectively (P<0.05). When 6-hydroxydopamine (6OHDA; 20 mg/kg i.v.) was given 3 days prior to the experiment, the protective effect of reserpinc was not evident. When bretylium (20 mg/kg i.v., 2 h prior to ouabain) was administered to animals previously treated with reserpine, the dose of ouabain which produced premature ventricular contractions, ventricular tachycardia, and death was increased to 109.0 ± 72 146.1 ± 12.6; and 165.8 ± 7.6 μg/kg, respectively (P<0.05). However, the magnitude of this protective action was similar to that produced by rcserpine alone. Lathers et al. (Fed. Proc. 40, 672, 1981) reported that bretylium alone provides protection of a similar order of magnitude as reserpine. Thus, the effects of rescrpine and bretylium were not additive: this indicates that the two agents may be acting on the same locus or they may be acting at different sites with the action of one drug masking or blocking the action of the other. Since 60HDA prevented the action of rcserpine on ouabain-induced ventricular arrhythmia and since 60HDA only produces degeneration of adrenergic nerve terminals, it is probable that the protective effect of both reserpine and bretylium is due to an action at the adrenergic nerve terminal. The heart rate and blood pressure were not involved in the antiarrhythmic effects of rcserpine.

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Pharmacology & Pharmacy
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