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COMPARATIVE IN VIVO AND IN VITRO STUDY OF THE CARDIAC EFFECTS OF MIDALCIPRAN AND IMIPRAMINE *
Author(s) -
ROUET R.H.,
TISNEVERSAILLES J.,
ADAMANTIDIS M.M.,
VINCENT A.,
DUPUIS B.A.
Publication year - 1989
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1989.tb00454.x
Subject(s) - imipramine , pharmacology , anticholinergic , antidepressant , chemistry , medicine , in vivo , anesthesia , hippocampus , biology , alternative medicine , pathology , microbiology and biotechnology
Summary— 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 ED 50 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 V max was significant at 3times10 −6 M for imipramine and 1times10 −5 M for midalcipran in normal (4 mM K+) and hyperpolarizing (2.7 mM K+) conditions. At the concentration of 1times10 −5 M midalcipran significantly lengthened, whereas imipramine non significantly shortened the action potential durations (APD 50 , APD 90 ). 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.