Antibacterial effect of four phenothiazines

Various types of phenothiazines were examined for antibacterial effect on 61 Gram-positive and Gram-negative bacterial strains in vitro. The investigated phenothiazines were two neuroleptic drugs, fluphenazine and chlorpromazine, and two antihistaminic drugs, alimemazine and promethazine. All four drugs have antibacterial effects in vitro, the phenothiazines being more potent against the Gram-positive microorganisms. The antibacterial potency of the drugs was measured as IC50: Fluphenazine 29 microM (15 micrograms/ml), alimemzaine 49 microM (37 micrograms/ml), promethazine 88 microM (28 micrograms/ml) and chlorpromazine 92 microM (29 micrograms/ml). The antibacterial potency of the drugs was linked neither to the neuroleptic nor the antihistaminic potency of the drugs, which is in agreement with results of earlier stereoisomeric investigations. Thus, the known phenothiazines may represent a pool of potentially new antimicrobial drugs. A therapeutic application of these results, however, requires additional in vitro an in vivo testing in an animal model. The bacterial model might be of value as a model system in the study of the interaction of neuropharmacological agents and other membrane active compounds on biological membranes.