The effect of phenothiazines and their metabolites on prostaglandin production by rat basophilic leukemia cells in culture.
Seven clinically important phenothiazine drugs (chlorpromazine, promazine, triflupromazine, thioridazine, fluphenazine, trifluoperazine and perphenazine) stimulated synthesis of PGE2 and PGF2alpha in RBL-1 cells in culture. Structural differences in the side chain at N10 had little effect on their activities. Some of the metabolites also were active, in keeping with the clinical observation that phenothiazines may have antipsychotic effects long after the parent compound has been eliminated from the circulation. Among the chlorpromazine metabolites, methoxy substituents on the phenothiazine nucleus did not strikingly affect stimulating activity. Monohydroxy derivatives were slightly more effective than the parent compound; there was little difference between hydroxy substitution at 7 or 8 position. The 7,8 dioxo, the N-oxido, the sulfoxide, and the 7-OH glucuronide derivatives were inactive.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001491:Basophils; D002478:Cells, Cultured; D015237:Dinoprost; D015232:Dinoprostone; D007942:Leukemia, Experimental / Q000378:metabolism*; D010640:Phenothiazines; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis*; D051381:Rats; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010640:Phenothiazines; D011458:Prostaglandins E; D011460:Prostaglandins F; D015237:Dinoprost; D015232:Dinoprostone