The antibacterial activity of the psychopharmacological agent clopenthixol and its two main metabolites.
The antibacterial effect of the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol and the two main metabolites of clopenthixol in man, N-dealkyl-clopenthixol and clopenthixol sulfoxide, was examined in 24 Gram-positive and 37 Gram-negative bacterial strains in vitro. The antibacterial potency of the drugs towards the Gram-positive strains, measured as IC50, was: N-dealkyl-clopenthixol, 6.2 microM (3.7 micrograms/ml), trans(E)-clopenthixol, 16 microM (7.6 micrograms/ml) and cis(Z)-clopenthixol, 37 microM (17.5 micrograms/ml), and clopenthixol sulfoxide was inactive in the investigated area. Against the Gram-negative strains the drugs are less potent. A therapeutic application of these results, especially in the case of trans(E)-clopenthixol, which possesses no neuroleptic activity, requires in vivo testing in an animal model. However, the in vitro model employed might also be useful in the study of such agents and other membrane-active compounds with regard to their interaction with biological membranes.
Department of Antibiotics, Statens Seruminstitut, Copenhagen, Denmark.
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Mortensen
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Kristiansen
D000900:Anti-Bacterial Agents; D003006:Clopenthixol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013892:Thioxanthenes / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D013892:Thioxanthenes; D003006:Clopenthixol