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Comparative in vivo and in vitro study of the cardiac effects of midalcipran and imipramine.

Authors :
Rouet RH
Tisne-Versailles J
Adamantidis MM
Vincent A
Dupuis BA
Source :
Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 1989; Vol. 3 (3), pp. 237-44.
Publication Year :
1989

Abstract

Midalcipran is a new antidepressant drug inhibiting both noradrenaline and serotonin uptake without any postsynaptic and anticholinergic activities. Its cardiac effects were compared with those of imipramine, a tricyclic antidepressant drug. In anaesthetised guinea-pigs intravenous perfusion of imipramine and midalcipran (1 ml/min from a solution at 0.66 mg/ml) brought about ventricular arrhythmias, respectively at 16.5 and 26.4 mg/kg and cardiac arrest at 58 and 97 mg/kg. The safety index (ratio of i.v. lethal dose and ED50 evaluated by the yohimbine test) is 22 times wider for midalcipran than imipramine. In in vitro studies on guinea-pig ventricular myocardium, imipramine exerted a greater class 1 antiarrhythmic effect than midalcipran. The reduction of Vmax was significant at 3 X 10(-6) M for imipramine and 1 X 10(-5) M for midalcipran in normal (4 mM K+) and hyperpolarizing (2.7 mM K+) conditions. At the concentration of 1 X 10(-5) M midalcipran significantly lengthened, whereas imipramine non significantly shortened the action potential durations (APD50, APD90). The results provide confirmation of a lesser depression in sodium conductance with midalcipran as compared to imipramine. Therefore it is proposed that less adverse cardiac effects may be observed at therapeutic doses.

Details

Language :
English
ISSN :
0767-3981
Volume :
3
Issue :
3
Database :
MEDLINE
Journal :
Fundamental & clinical pharmacology
Publication Type :
Academic Journal
Accession number :
2767606
Full Text :
https://doi.org/10.1111/j.1472-8206.1989.tb00454.x