Phenothiazine compounds inhibit in vitro growth of pathogenic free-living amoebae

The phenothiazine compounds trifluoperazine dihydrochloride and chlorpromazine hydrochloride have in vitro activity against the pathogenic free-living amoebae Naegleria fowleri, Acanthamoeba culbertsoni, and Acanthamoeba polyphaga. Drug concentrations of 10 microM were amoebastatic; concentrations of 50 microM were either amoebastatic or amoebicidal. Concentrations of 100 microM were generally amoebicidal. The mechanism of drug action is unclear. It may reflect sensitivity of amoeba calcium regulatory protein to the phenothiazine compounds or may be due to the lipophilic action of the drugs on the amoeba plasma membrane. Accumulation of these drugs in the central nervous system makes them potentially useful chemotherapeutic agents in humans for treatment of amoebic meningoencephalitis caused by N. fowleri and Acanthamoeba spp.