Abstract
Groups of rats were treated orally with increasing doses of quinidine and maprotiline alone, and in combination. Serial electrocardiograms were recorded. Both drugs caused increases in PQ and QRS intervals, but had no effect on heart rate. After discontinuation of treatment the ECG changes disappeared promptly in maprotiline-, and slowly in quini-dine-treated animals. The combined treatment induced bradycardia, more pronounced increases in PQ and QRS intervals, prolongation of the QT interval and increase of S wave amplitude. The additive effects of the two drugs are explained by their nonspecific action on cell membranes (“membrane-stabilizing effect”). It is concluded that the combined use of quinidine and other Type I antiarrhythmic drugs and tricyclic antidepressants increases the risk for cardiovascular side-effects.
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References
Bianchetti G, Bonaccorsi A, Chiodaroli A, Franco R, Garattini S, Gomeni R, Morselli PL (1977) Plasma concentrations and cardiotoxic effects of desipramine and protriptyline in the rat. Br J Pharmacol 60: 11–19
Bigger JT Jr, Kantor SJ, Glassman AH, Perl JM (1978) Cardiovascular effects of tricyclic antidepressant drugs. In: Lipton MA, DiMascio A, Killam KF (eds) Psychopharmacology: a generation of progress. Raven Press, New York, pp 1033–1046
Brunner H, Hedwall PR, Bein HJ (1971) Cardiovascular effects of preparation CIBA 34,276-Ba and imipramine. Agents Act 2: 69–82
Burckhardt D, Fleischhauer HJ, Müller V, Neubauer HW (1976) Beitrag zur Wirkung tri- und tetrazyklischer Antidepressiva auf Herz und Kreislauf. Schweiz Med Wochenschr 106: 1896–1903
Callaham M (1979) Tricyclic antidepressant overdose. JACEP 8: 413–425
Deglin SM, Deglin JM, Chung EK (1977) Drug-induced cardiovascular diseases. Drugs 14: 29–40
Elonen E (1974) Correlation of the cardiotoxicity of tricyclic antidepressants to their membrane effects. Med Biol 52: 415–423
Eisner J, Knutti R (1981) The graphical representation of the time evolution of ECG data using a computer data storage and plot package. In: Budden R, Detweiler D, Zbinden G (eds) The rate lectrocardiogram in pharmacology and toxicology. Pergamon Press, Oxford, pp 161–170
Giardina EGV, Bigger JT Jr, Glassman AH, Perel JM, Kantor SJ (1979) The electrocardiographic and antiarrhythmic effects of imipramine hydrochloride at therapeutic plasma concentrations. Circulation 60: 1045–1052
Grauwiler J (1965) Herz und Kreislauf der Säugetiere. Birkhäuser Verlag, Basel und Stuttgart
Jefferson JW (1975) A review of the cardiovascular effects and toxicity of tricyclic antidepressants. Psychosom Med 37: 160–179
Langslet A, Johansen WG, Ryg M, Skomedal T, Oxy I (1971) Effects of dibenzepine and imipramine on the isolated rat heart. Eur J Pharmacol 14: 333–339
Lechat P, Auclair MC, Adolphe M (1974) Effect of imipramine on cultured heart cells. Toxicol Appl Pharmacol 27: 336–341
Marmo E, Coscia L, Cataldi S (1972) Cardiac effects of antidepressants. Jpn J Pharmacol 22: 283–292
Nawrath H (1981) Action potential, membrane currents and force of contraction in mammalian heart muscle fibres treated with quinidine. J Pharmacol Exp Ther 216: 176–182
Roberts J, Stadter RP, Cairoli V, Modell W (1962) Relationship between adrenergic activity and cardiac actions of quinidine. Circ Res 11: 758–764
Schmitt H, Cheymol G, Gilbert JC (1970) Effets anti-arythmisants et hémodynamiques de l'imipramine et de la chlorimipramine. Arch Int Pharmacodyn 184: 158–174
Theisen K, Jahrmärker H (1975) Re-entry Mechanismus ventrikulärer Tachykardien bei inhomogener Repolarisation. Dtsch Med Wochenschr 100: 1141–1147
Winsberg BG, Goldstein S, Yepes LE, Perel JM (1975) Imipramine and electrocardiographic abnormalities in hyperactive children. Am J Psychiatry 132: 542–545
Zbinden G (1981) Assessment of cardiotoxic effects in subacute and chronic rat toxicity studies. In: Balazs T (ed) Cardiac Toxicity, vol III. CRC Press Inc, Boca Raton, FL pp 7–32
Zbinden G, Ettlin R, Bachmann E (1980) Electrocardiographic changes in rats during chronic treatment with antidepressant and neuroleptic drugs. Arzneim Forsch 10: 1709–1715
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Zbinden, G., Spichiger, H. Subchronic toxicity study of quinidine and maprotiline alone, and in combination in rats. Arch Toxicol 51, 43–51 (1982). https://doi.org/10.1007/BF00279320
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DOI: https://doi.org/10.1007/BF00279320