Possible Interaction: Chlorpromazine and Melatonin

“The addition of CPZ during the horseradish peroxidase (HRP)‐catalyzed oxidation of melatonin provoked a significant increase in the rate of oxidation and production of N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK).”

“The effect of CPZ on melatonin oxidation was rather higher at alkaline pH. At pH 9.0, the efficiency of oxidation of melatonin was 15 times higher and the production of AFMK was 30 times higher as compared with the assays in the absence of CPZ.”

“We suggest that CPZ is able to exacerbate the rate of oxidation of melatonin by an electron transfer mechanism where CPZ•+, generated during the peroxidase‐catalyzed oxidation, is able to efficiently oxidize melatonin.”

“Instead, chlorpromazine , the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.”

“A similar effect was reported in rats (Wurtman & others, 1968) when chlorpromazine increased serum melatonin concentration five-fold.”

“ Chlorpromazine , which elevates plasma melatonin in man and rat, significantly reduced melatonin\ turnover and reduced the formation of both metabolites in control and phenobarbitone induced microsomes.”

“With benzpyrene induction, chlorpromazine inhibited melatonin turnover but in this group, 6-hydroxymelatonin concentrations were higher than controls.”

“A dose-dependent decrease was observed for melatonin content in the administration of diazepam (DZP), hydroxyzine (HYZ), chlorpromazine (CPZ) or haloperidol (HPD).”

“ Chlorpromazine (25.0 mg kg −1 ), which may block the breakdown of endogenous melatonin , also caused a significant decline in MST.”

“Pretreatment with chlorpromazine slowed the disappearance of exogenous melatonin from rat plasma and markedly raised the concentrations of endogenous melatonin in both the pineal gland and the plasma.”