Since phenothiazines alter antibiotic susceptibility of microorganisms by inhibiting efflux pumps, are these agents useful for evaluating similar pumps in phenothiazine-sensitive parasites?

Phenothiazines have activity against Schistosoma mansoni, Trypanosoma brucei, Trypanasoma gambiensi, Molinema dessetae, Leishmania spp., Plasmodium falciparum and free-living protozoa. These organisms and other parasitic infections are prevalent in HIV-infected humans. These infections are becoming more frequently resistant to commonly employed antibiotics, and due to the absence of economic motivation, new and effective compounds against these infections are not anticipated in the near future. Resistance of prokaryotes and eukaryotes to antibiotics is now known to be also due to the presence of efflux pumps that extrude the antibiotic prior to the agent reaching its target. Because phenothiazines are known to inhibit some efflux pumps and therefore alter the susceptibility of the organism to an antibiotic to which it is resistant, and also because of the sensitivity of the above parasites to phenothiazines, efflux pumps may play a role in emerging antibiotic resistance of these organisms. Furthermore, their prevalence is known to be greatest in areas that have high rates of HIV infection; therefore, it would be necessary that these agents should receive close scrutiny. This review concerns the attributes afforded by phenothiazines related to their effective activity against a wide range of parasites. Because these agents are inexpensive and many are no longer protected by patent, they may be exploited as anti-parasitic agents in the poorer areas of the world.