The anti-influenza virus drug rimantadine has trypanocidal activity

Abstract

We report here that bloodstream forms of the African trypanosome, Trypanosoma brucei, are sensitive to the anti-influenza virus drug rimantadine (50% inhibitory concentration of 1.26 micrograms ml-1 at pH 7.4). The activity is pH dependent and is consistent with a mechanism involving inhibition of the ability to regulate internal pH. Rimantadine is also toxic to the trypanosomatid parasites Trypanosoma cruzi and Leishmania major.

FIG. 1

Susceptibility of bloodstream form T. brucei (A), T. cruzi epimastigotes (B), and L. major promastigotes (C) to rimantadine at different pHs. Parasites were cultured as described in the text in the presence or absence of 2 μg of rimantadine ml⁻¹ (A) or 20 μg of rimantadine ml⁻¹ (B, C). In the case of T. brucei, treatment with 20 μg of rimantadine ml⁻¹ resulted in total cell death at each pH tested. Values are expressed as a percentage of growth obtained at optimal pH in the absence of drug.