Antileishmanial activity of the antiulcer agent omeprazole.

The benzimidazole compound omeprazole, used widely for the treatment of peptic ulcer disease, inhibits the growth of Leishmania donovani, the causative agent of visceral leishmaniasis. Promastigotes cultured at acidic pH and amastigotes within infected macrophages are reduced 90% or more with 150 microM omeprazole. Antiparasitic action of the drug is due to its inhibition of the P-type K(+),H(+)-ATPase on the surface membrane. This enzyme is important for pH homeostasis and the maintenance of proton motive force across the membrane in Leishmania. The drug is effective only at acidic pH, a condition that mimics the in vivo environment within the phagolysosomal vesicles where the amastigote form of the parasite resides. Omeprazole deserves consideration as an alternative to currently available chemotherapeutics, which have severe toxic side effects.