Chlorpromazine: A Drug Potentially Useful for Treating Mycobacterial Infections

TLDR

Chlorpromazine, a phenothiazine, has documented antimicrobial activity against mycobacteria and was historically reported to improve tuberculosis outcomes. The study aimed to evaluate chlorpromazine’s capacity to inhibit replication of *Mycobacterium tuberculosis* and *Mycobacterium avium* in cultured normal human macrophages by measuring viable bacterial counts at 0, 4, and 7 days post‑infection. Researchers further assessed chlorpromazine’s synergistic potential with standard antimycobacterial agents—including isoniazid, streptomycin, pyrazinamide, rifampin, rifabutin, penicillin, and ethambutol—against intracellular mycobacteria. Chlorpromazine inhibited intracellular mycobacteria at 0.23–3.6 µg/ml, was more effective inside macrophages than extracellularly, and enhanced the activity of most tested drugs except ethambutol.

Abstract

Chlorpromazine (CPZ) is one of several phenothiazines known to have antimicrobial properties. It can inhibit mycobacteria, and was reported in the early literature to improve tuberculosis clinically. CPZ was tested here for its ability to inhibit the replication of Mycobacterium tuberculosis and Mycobacterium avium in cultured normal human macrophages, as determined by counts of viable bacteria at 0,4, and 7 days after bacterial infection of the macrophages. CPZ inhibited the intracellular bacteria at a concentration range of 0.23-3.6 μg/ml, and was more effective intracellularly than extracellularly. It was further tested for its ability to cooperate with isoniazid, streptomycin, pyrazinamide, rifampin, rifabutin, penicillin and ethambutol (EMB) against intramacrophage M. tuberculosis and M. avium. CPZ enhanced the effectiveness of most of the drugs tested against intracellular mycobacteria. However, the combination of CPZ and EMB did not result in augmented antimycobacterial activity.