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Comparative in vivo and in vitro study of the cardiac effects of midalcipran and imipramine.
- 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.
- Subjects :
- Action Potentials drug effects
Animals
Electrophysiology
Female
Guinea Pigs
In Vitro Techniques
Infusions, Intravenous
Male
Membrane Potentials drug effects
Milnacipran
Myocardial Contraction drug effects
Papillary Muscles drug effects
Potassium pharmacology
Antidepressive Agents pharmacology
Cyclopropanes pharmacology
Heart drug effects
Imipramine pharmacology
Subjects
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