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Cardiotoxic actions of doxepin and barium chloride in conscious rabbits
Abstract:
Infusion of doxepin (Dx) i.v. to conscious rabbits induced dose dependently cardiac dysrhythmias of varying severity. Attempts to reduce sympathetic tone with diazepam or clonidine failed to modify Dx effects. Activation of the heart with aminophylline sensitized the animals to Dx effects. Infusion of barium chloride (Ba) caused severe ventricular dysrhythmias which were promptly abolished or reduced by verapamil. A subtoxic dose of Dx, but not diazepam, clonidine or taurine, counteracted Ba effects. Both the toxic and "therapeutic" effects of Dx might depend on its "quinidine-like" membrane effects.
Insights
Doxepin infusion caused cardiac dysrhythmias in rabbits, and attempts to mitigate these effects were unsuccessful. However, doxepin counteracted barium chloride-induced dysrhythmias, suggesting quinidine-like membrane effects.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Doxepin is a tricyclic antidepressant with known cardiovascular side effects.
- Cardiac dysrhythmias are a significant concern with certain drug administrations.
Purpose of the Study:
- To investigate the cardiac effects of doxepin infusion in conscious rabbits.
- To explore potential counteracting agents and mechanisms for doxepin-induced dysrhythmias.
Main Methods:
- Intravenous infusion of doxepin in conscious rabbits.
- Administration of diazepam, clonidine, aminophylline, and barium chloride to assess interactions.
- Observation and recording of cardiac dysrhythmias.
Main Results:
- Doxepin induced dose-dependent cardiac dysrhythmias.
- Diazepam and clonidine did not alter doxepin's effects.
- Aminophylline sensitized rabbits to doxepin.
- Verapamil abolished barium chloride-induced dysrhythmias.
- Doxepin counteracted barium chloride-induced dysrhythmias.
Conclusions:
- Doxepin's toxic and potential therapeutic effects may stem from quinidine-like membrane actions.
- Sympathetic modulation is ineffective against doxepin-induced cardiac issues.
- Further research into doxepin's membrane effects is warranted.