Interaction studies between three antidepressant drugs (chlorimipramine, imipramine and zimelidine) and noradrenaline, tyramine and vagal stimulation on the heart rate and blood pressure in dogs.

Anaesthetized Beagle dogs were given increasing intravenous doses of imipramine, chlorimipramine or zimelidine. At each dose interval the interference of the drug administered with the effects on blood pressure and heart rate of vagal stimulation, NA injection and tyramine injection was investigated. Also, the in vitro uptake of 5-HT into platelets after in vivo administration to unanaesthetized dogs of 5 mg chlorimipramine or 5 mg zimelidine was studied. Chlorimipramine and zimelidine were found to be about equipotent as regards 5 HT-uptake into platelets after in vivo administration. Imipramine and chlorimipramine potentiated the effects of NA after the 2 mg/kg dose. Imipramine but not chlorimipramine interfered with the effects of tyramine after the 4 mg/kg dose. Zimelidine did not interfere with either NA or tyramine at any dose level studied (maximal cumulative dose 62 mg/kg). The effect of vagal stimulation was significantly inhibited after 8 mg/kg (cumulative dose 14 mg/kg) of imipramine and 16 mg/kg (cumulative dose 30 mg/kg) of chlorimipramine and zimelidine, respectively. It is concluded that zimelidine in comparison with imipramine and chlorimipramine has no or at most a slight effect on peripheral adrenergic neurones. It has less pronounced anticholinergic properties than imipramine but is about equipotent to chlorimipramine in this respect.