In vivo and in vitro studies on the effects of some phenothiazines and sulpiride on kynurenine metabolism.
The effect of 5 consecutive daily i.p. doses of CPZ (5 mg/kg), PZ (10 mg/kg) and PMZ (10 mg/kg) on the activity of kynurenine hydrolase and kynurenine aminotransferase in mouse liver was studied. All three phenothiazines effected an increase in the activity of kynurenine hydrolase per unit weight of liver with CPZ showing the highest activation followed by PZ and PMZ. On the other hand kynurenine aminotransferase was more moderately inhibited by the above treatment. In vitro studies showed that the phenothiazines tested and the pharmacologically inactive CPZO, the major metabolite of CPZ, in concentrations ranging from 3 X 10(-9) to 3 X 10(-4) M had an activating effect on kynurenine hydrolase. Increases in activity were obtained up to concentrations of 3 X 10(-6) M and levelled off afterwards. The highest increases were observed with CPZ and CPZO, while those of PZ and PMZ were of lesser magnitude. However, the tested phenothiazines were without effect on kynurenine aminotransferase. The newly introduced psychotropic drug, sulpiride, which is a substituted benzamide, was devoid of activity on either enzyme both in vivo (50 mg/kg) and in vitro (3 X 10(-9) to 3 X 10(-4) M).
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D006867:Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D007737:Kynurenine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008190:Lyases; D008297:Male; D010640:Phenothiazines; D051381:Rats; D013469:Sulpiride / Q000494:pharmacology*; D000637:Transaminases / Q000378:metabolism
D014150:Antipsychotic Agents; D010640:Phenothiazines; D007737:Kynurenine; D013469:Sulpiride; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D006867:Hydrolases; C021480:kynureninase; D008190:Lyases