Summary
The effects on the heart rate and ECG of anaesthetised guinea-pigs of amitriptyline, doxepin, imipramine and nortriptyline infused at 1.0 mg/kg/min until death were observed. In addition an in vitro study on guinea-pig atria was performed on the chronotropic and inotropic effects of these drugs and of desmethylimipramine and protriptyline at a concentration of 10−5 M. The effect of sodium bicarbonate (3 mEq/kg i.v.) and propranolol (0.01–0.2 mg/kg i.v.) on amitriptyline and doxepin induced ECG changes was also assessed.
A difference in the cardiac effects of the in vivo and in vitro model was observed. Guinea-pigs infused with doxepin survived significantly longer than those infused with amitriptyline, imipramine or nortriptyline. No statistically significant difference was found between the tricyclic drugs with respect to onset of widening of the QRS complex, increased PR and QT intervals. In the spontaneously beating atrial preparation doxepin was the most potent cardio-depressant. Sodium bicarbonate had no effect on arrhythmias induced by tricyclics, while propranolol, apart from the bradycardia induced, was without beneficial effect on the ECG.
The guinea-pig provides a good model for studying the arrhythmogenic actions of tricyclic antidepressants.
Zusammenfassung
Untersucht wurden die Wirkungen intravenöser Infusionen (1.0 mg/kg/min bis zum Erreichen der tödlichen Dosis) von Amitriptylin, Doxepin, Imipramin und Nortriptylin auf die Herzfrequenz und das EKG betäubter Meerschweinchen. Außerdem wurden an isolierten Meerschweinchen-Vorhöfen in vitro die chronotropen und inotropen Effekte dieser Substanzen sowie von Desmethylimipramin und Protriptylin bei einer Konzentration von 10−5 M geprüft. Schließlich interessierte auch der Einfluß von Natriumbicarbonat (3 mÄq/kg i.v.) und Propranolol (0,01–0,2 mg/kg i.v.) auf die durch Amitriptylin und Doxepin ausgelösten EKG-Veränderungen.
Die cardialen Effekte der Antidepressiva zeigen am in vivo und in vitro- Modell Unterschiede. Die mit Doxepin infundierten Meerschweinchen wiesen eine signifikant längere Überlebenszeit auf als die mit Amitriptylin, Imipramin und Nortriptylin behandelten. Hinsichtlich des Eintritts der Verbreiterung des QRS-Komplexes, sowie der Verlängerung der PR- und QT-Intervalle zeigten die einzelnen tricyclischen Antidepressiva keine Unterschiede. Am spontanschlagenden Vorhofpräparat hatte Doxepin die stärkste cardiodepressive Wirkung. Natriumbicarbonat hatte keine Wirkung auf die durch die Antidepressiva ausgelösten Arrythmien, während Propranolol — abgesehen von der Bradycardie-Auslösung — keine günstige Wirkung auf das EKG besaß.
Das Meerschweinchen stellt ein gutes Modell zum Studium der Arrythmie erzeugenden Wirkungen von tricyclischen Antidepressiva dar.
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Dumovic, P., Burrows, G.D., Vohra, J. et al. The effect of tricyclic antidepressant drugs on the heart. Arch Toxicol 35, 255–262 (1976). https://doi.org/10.1007/BF00570267
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DOI: https://doi.org/10.1007/BF00570267
Key words
- Amitriptyline
- Desmethylimipramine
- Doxepin
- Imipramine
- Nortriptyline
- Protriptyline
- Intoxication
- Guinea pig
- ECG
- Propranolol
- Sodium bicarbonate