Serotonin Now: Clinical Implications of Inhibiting Its Synthesis with Para-Chlorophenylalanine

Abstract

Some of the mystery surrounding serotonin has been unraveled recently after the development of a means of selectively depriving the organism of this amine. Key aspects of recent advances include biochemical characterization of the first enzymatic step in tissue serotonin biosynthesis, that of tryptophan 5-hydroxylation; discovery of an inhibitor (para-chlorophenylalanine (PCPA)) of the reaction; and observations on the effects of serotonin deprival as produced by PCPA in man and animals. Control of diarrhea in the carcinoid syndrome by PCPA treatment indicates that the major target organ of circulating serotonin is the intestinal tract. Induction of psychiatric effects with high doses of PCPA, along with other evidence, is compatible with a serotonin-deficiency hypothesis of affective illness. Serotonin plays a role in sleep mechanisms, with PCPA suppressing and 5-hydroxytryptophan (serotonin precursor) restoring rapid eye movement sleep in man. Finally, animal data raise exciting possibilities of the involvement of brain serotonin in control of sexual behavior. The serotonin-deprival approach has only begun to be explored in clinical pathophysiologic states.