RT Journal Article SR Electronic T1 Tryptophan Hydroxylase Inhibition: the Mechanism by Which p-Chlorophenylalanine Depletes Rat Brain Serotonin JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 274 OP 278 VO 3 IS 3 A1 JÉQUIER, ERIC A1 LOVENBERG, WALTER A1 SJOERDSMA, ALBERT YR 1967 UL http://molpharm.aspetjournals.org/content/3/3/274.abstract AB Administration of the specific serotonin depletor p-chlorophenylalanine to rats results in marked inhibition of tryptophan hydroxylase of the brain. The enzyme inhibition can be correlated with and is assumed to be responsible for brain serotonin depletion. Although p-chlorophenylalanine is a competitive inhibitor of tryptophan hydroxylase in vitro, it causes an irreversible inactivation of the enzyme in vivo. The findings also support the conclusion that tryptophan hydroxylation is the rate-limiting enzymic step in serotonin biosynthesis. ACKNOWLEDGMENT The authors would like to thank Dr. Sidney Udenfriend for helpful discussions during the course of this work.