Haemodynamic effects of pirlindole, a new tetracyclic antidepressant agent

Cardiovascular dynamic, inotropic and electrophysiologic effects of the new tetracyclic antidepressant 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]-carbazole hydrochloride (pirlindole) (0.5, 1, 2.5, 5 and 10 mg/kg, i.v.) were investigated in anaesthetized dogs and compared with those of i.v. imipramine (0.5, 1, 2.5 and 5 mg/kg) administration. Noradrenaline (norepinephrine)-induced systemic blood pressure increase was significantly potentiated by imipramine but not by pirlindole. Severe hypotension was caused by most imipramine doses, whereas the initial blood pressure fall after pirlindole was followed by an increase. Heart rate did not alter with lower prilindole doses but increased after 2.5 mg/kg. Imipramine caused severe tachycardia. Pirlindole had no effects on contractility but imipramine was negative-inotropic. Left ventricular end-diastolic pressure fell after pirlindole; imipramine caused transient decrease in filling pressure between 0.5 and 2.5 mg/kg, whereas 5 mg/kg significantly elevated this variable. Myocardial oxygen consumption increased with 5 and 10 mg/kg pirlindole but was reduced by imipramine. Pirlindole did not induce changes in the electrophysiology of the heart. Imipramine decreased PQ-time and elevated ST-T segments indicating myocardial ischaemia. Imipramine effects on electrical conduction were deleterious so that no dog survived 10 mg/kg. These results suggest that pirlindole may be a possible therapeutic regimen for treatment of depressed human patients with a previous history of cardiovascular disease.