INHIBITION OF THE METABOLISM OF H3-MELATONIN BY PHENOTHIAZINES

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland, and Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts

After rats are treated acutely with chlorpromazine, there is an elevation in the level of i.v. administered H³-melatonin in brain and blood. This effect is not the result of the hypothermia produced by chlorpromazine. Other phenothiazines, such as promazine and promethazine, also elevate tissue H³-melatonin. Chlorpromazine has no effect on the level of H³-melatonin when the indole is administered to rats by injection into the lateral cerebral ventricle. Chlorpromazine inhibits the in vitro metabolism of H³-melatonin by liver slices, suggesting that the drug alters the tissue levels of the indole by slowing its metabolism. Chronic treatment with phenobarbital causes a decreased H³-melatonin concentration in the brain 30 min after i.v. injection of the indole.