Antidepressants Cause Lethal Disruption of Membrane Function in the Human Protozoan Parasite Leishmania

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Abstract
The antidepressant compounds clomipramine and nitroimipramine were cidal to extracellular promastigotes of both human protozoan parasites L. donovani and L. major. Clomipramine also killed amastigotes of both species within murine macrophages with no apparent toxicity to the host cells. Amastigotes were more sensitive than promastigotes to clomipramine. Clomipramine (100 .mu. per l or 0.2 nmol per 1 .times. 106 cells) inhibited L-proline transport in promastigotes. Synergistic inhibition of L-proline transport was observed with clomipramine after addition of either of the ionophores valinomycin or nigericin. The cytotoxic effects of clomipramine evidently result from its disruption of the proton electrochemical gradient of the parasite surface membrane.