Effects on haemodynamics and plasma noradrenaline levels in man of long term treatment with imipramine, haloperidol and chlorpromazine

Abstract

Haemodynamic effects in patients treated with imipramine and haloperidol were studied at rest and during exercise and were related to the arterial plasma levels of noradrenaline. The results were compared with earlier observations on untreated and chlorpromazine-treated patients studied by the same techniques. After imipramine in a daily dose of 150–350 mg, there was a tendency for the heart rate to increase but no other particular haemodynamic effects were observed. During imipramine treatment noradrenaline levels were not increased compared to the controls, at a work load of less than 900 kpm/min, after which there appeared to be some increase. After haloperidol in a dose of 12–22 mg per day no changes were observed in the circulation or plasma noradrenaline levels. More marked effects on the circulation and plasma noradrenaline levels were found in patients treated with very large doses of chlorpromazine (1800–3600 mg daily). They showed a lower cardiac output, stroke volume and systolic and mean arterial blood pressure during exercise than the other groups. In the chlorpromazine-treated group the heart rate was higher both at rest and during mild exercise. The plasma noradrenaline levels were higher at rest and at all work loads than in the other patients. It may be concluded that the haemodynamic effects of chlorpromazine and its effects on the plasma noradrenaline levels are primarily due to its peripheral α-adrenergic receptor blocking effect, which induces a compensatory increase in sympathetic nerve impulse flow. However, an increased overflow of noradrenaline from the nerve terminals per nerve impulse due to drug effects at the nerve terminal-effector cell level might also contribute to the high plasma levels of noradrenaline found after chlorpromazine treatment.