Effect of some psychotropic drugs on the activated macrophage-induced luminol-dependent chemiluminescence.

The effect of some psychotropic drugs on the activity of macrophages to produce superoxide radicals during phagocytosis was tested. Three-cyclic antidepressants, imipramine and amitriptyline, and the thioxanthene neuroleptic, chlorprothixene, were studied. The superoxide production was measured by luminol-dependent chemiluminescence. The drugs were investigated in the concentration range of 10(-7)-10(-4) mol/l. It was seen that all tested drugs caused a concentration-dependent decrease of the luminol-dependent chemiluminescence. The inhibitory effect of imipramine and amitriptyline on the macrophage superoxide production was moderate, while the effect of chlorprothixene was significantly stronger (a decrease more than 100 times that of macrophage chemiluminescence). Essentially, the luminol-dependent chemiluminescence reflects the level of superoxide radicals in the system. Therefore, the effect of drugs may be due to the possible activity for scavenging superoxide. In additional experiments with different systems of generations of O2- and different methods of registration, this possibility was discarded. Therefore, the effect of the drugs on the luminol-dependent chemiluminescence seems to be due to drug-induced decrease of the ability of activated macrophages to produce superoxide radicals.

Effect of phenothiazines on activated macrophage-induced luminol-dependent chemiluminescence.

The inhibitory effect of some phenothiazine neuroleptics (chlorpromazine, levomepromazine, thioridazine, promethazine and trifluoperazine) on the ability of rat peritoneal macrophages to produce O2- during phagocytosis was investigated. The superoxide radical release was estimated by measuring the luminol-dependent chemiluminescence (CL). The effect of drugs was studied in the concentration range of 0.1-100 mumol/l. Additional experiments to determine the ability of the drugs to scavenge O2- were carried out. They included measuring the effect of phenothiazines on the luminol-dependent CL in systems with enzymatically (xanthine-xanthine oxidase) and non-enzymatically (KO2) generated O2-. The ability of phenothiazines to scavenge O2- was additionally tested by a "non-luminescence" method in which the superoxide concentration was determined spectrophotometrically by the reduction of nitro blue tetrazolium to formazan. All drugs tested decreased significantly CL of stimulated macrophages at concentrations greater than 1 mumol/l. The C50 values were between 0.45 and 1.74 mumol/l. Also phenothiazines were found to act as scavengers of O2-. However, this effect occurred at significantly higher drug concentrations. The C50 values for 50% scavenging of O2- in systems with different sources of O2- were in the concentration range of 5-160 mumol/l. These results suggested that phenothiazines predominantly affected the ability of macrophages to produce O2- during phagocytosis. The findings may provide some insight into the untoward effects of the drugs tested.