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Science 23 November 1984:
Vol. 226. no. 4677, pp. 977 - 979
DOI: 10.1126/science.6505677
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Articles

Science, Vol 226, Issue 4677, 977-979
Copyright © 1984 by American Association for the Advancement of Science

articles

Antidepressants cause lethal disruption of membrane function in the human protozoan parasite Leishmania

D Zilberstein and DM Dwyer

The antidepressant compounds clomipramine and nitroimipramine were cidal to extracellular promastigotes of both human protozoan parasites Leishmania donovani and Leishmania major. Clomipramine also killed amastigotes of both species within murine macrophages with no apparent toxicity to the host cells. Further, amastigotes were more sensitive than promastigotes to clomipramine. Clomipramine (100 micromoles per liter or 0.2 nanomole per 1 X 10(6) 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. These observations suggest that the cytotoxic effects of clomipramine result from its disruption of the proton electrochemical gradient of the parasite surface membrane.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Biochemical Changes During Clomipramine Treatment of Childhood Obsessive-Compulsive Disorder.
M. F. Flament, J. L. Rapoport, D. L. Murphy, C. J. Berg, and C. R. Lake (1987)
Arch Gen Psychiatry 44, 219-225
   Abstract »    PDF »
Perturbation of red cell membrane structure during intracellular maturation of Plasmodium falciparum.
T. Taraschi, A Parashar, M Hooks, and H Rubin (1986)
Science 232, 102-104
   Abstract »    PDF »
Antiprotozoal activity of tricyclic compounds.
E. Hewlett, R. Pearson, D Zilberstein, and D. Dwyer (1985)
Science 230, 1063-1064
   PDF »
Antiprotozoal activity of tricyclic compounds.
D. ZILBERSTEIN and D. M. DWYER (1985)
Science 230, 1064
   PDF »


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