Thioridazine: resurrection as an antimicrobial agent?

Abstract

The emergence of multiresistant bacterial strains and the continuing burden of infectious disease globally point to the urgent need for novel affordable antimicrobial drugs. Thioridazine is a phenothiazine antipsychotic drug with well-recognized antimicrobial activity, but this property has not been harnessed for clinical use as a result of its central nervous system and cardiac side-effects. The cardiotoxicity of thioridazine has recently been shown to be structurally specific at a molecular level, whereas its antimicrobial properties are shared by a number of phenothiazine analogues. This raises the possibility that its enantiomers or its inactive metabolite, the ring sulphoxide, may act as a lead compound in the future development of antimicrobial drugs to face the new challenges in infectious disease.

Figure 1

Metabolic pathway of thioridazine in man