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.