Effect of caroxazone, a new antidepressant drug, on monoamine oxidases in healthy volunteers.

Caroxazone is a new antidepressant drug with a reversible inhibitory effect on monoamine oxidases (MAO) as previously shown experimentally in animals. The effect of caroxazone on MAO was explored in healthy volunteers and compared with that of tranylcypromine and imipramine. Daily urinary excretion of tryptamine and MAO activity in platelets were assayed at various times during and after treatment and the differences from basal values were statistically analysed. In addition, caroxazone plasma levels were determined. Caroxazone administered orally at doses of 300 or 600 mg/day for 12 days induced a significant, dose-dependent increase in urinary tryptamine excretion. Tranylcypromine (20 mg/day for 8 days) was even more active in this respect; imipramine (50 mg/day for 12 days) was completely inactive. MAO activity in platelets was not affected by caroxazone or imipramine, but was completely inhibited by tranylcypromine. Mean steady-state plasma levels of caroxazone were about 6 μg/ml and 11-12 μg/ml with the dose of 300 mg/day and 600 mg/day respectively. It can be concluded that caroxazone is a MAO inhibitor in man too, at a clinically effective dose such as 600 mg/day. The fact that its MAO inhibition is not apparent in platelet preparation may be explained by its reversibility. Tranylcypromine confirmed its potent irreversible MAO inhibitory effect, while imipramine lacked any effect at the tested dose.