In vitro modulation of human neutrophil chemotaxis by cis(Z)- and trans(E)-clopenthixol, and chlorpromazine.
Phenothiazines have been shown to depress several functions of neutrophils, including chemotaxis. A biphasic effect of chlorpromazine (CPZ) and other phenothiazines on human neutrophil chemotaxis has recently been described. We investigated the effect of the stereo-isomers of clopenthizol, a thioxanthene, and of CPZ on human neutrophil chemotaxis. CPZ, at a concentration of 157 microM, and cis(Z)- or trans(E)-clopenthixol, at 105 microM, decreased cell viability. Cis(Z)- and trans(E)-clopenthixol as well as CPZ exerted a biphasic effect on neutrophil chemotaxis with a maximal enhancement of 57%, 92%, and 119%, respectively, and inhibition at higher concentrations. Enhancement of human neutrophil chemotaxis and possibly of the antibacterial activity of these cells by CPZ and the stereo-isomeric compounds of clopenthixol may have clinical implications especially in immunocompromised hosts. The enhancing effect of trans(E)-clopenthixol is of particular importance as this stereo-isomer of clopenthixol exhibits both antimicrobial and antiplasmodial activity but has no antipsychotic or antihypersecretory effect.
D001424:Bacterial Infections / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology*; D003006:Clopenthixol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D013237:Stereoisomerism; D013892:Thioxanthenes / Q000494:pharmacology*
D013892:Thioxanthenes; D003006:Clopenthixol; D002746:Chlorpromazine