EFFECT OF PHENOTHIAZINES ON ACTIVATED MACROPHAGE-INDUCED LUMINOL-DEPENDENT CHEMILUMINESCENCE

The inhibitory effect of some phenothiazine neuroleptics (chlorpromazi ne, levomepromazine, thioridazine, promethazine and trifluoperazine) o n the ability of rat peritoneal macrophages to produce O-2(-) during p hagocytosis was investigated. The superoxide radical release was estim ated by measuring the luminol-dependent chemiluminescence (CL). The ef fect of drugs was studied in the concentration range of 0.1-100 mu mol /l. Additional experiments to determine the ability of the drugs to sc avenge O-2(-) were carried out. They included measuring the effect of phenothiazines on the luminol-dependent CL in systems with enzymatical ly (xanthine-xanthine oxidase) and non-enzymatically (KO2) generated O -2(-). The ability of phenothiazines to scavenge O-2(-) was additional ly tested by a ''non-luminescence'' method in which the superoxide con centration was determined spectrophotometrically by the reduction of n itro blue tetrazolium to formazan. All drugs tested decreased signific antly CL of stimulated macrophages at concentrations greater than 1 mu mol/l. The C-50 values were between 0.45 and 1.74 mu mol/l. Also phen othiazines were found to act as scavengers of O-2(-). However, this ef fect occurred at significantly higher drug concentrations. The C-50 va lues for 50% scavenging of O-2(-) in systems with different sources of O-2(-) were in the concentration range of 5-160 mu mol/l. These resul ts suggested that phenothiazines predominantly affected the ability of macrophages to produce O-2(-) during phagocytosis. The findings may p rovide some insight into the untoward effects of the drugs tested.