Clinical‐pharmacological evaluation of p‐chlorophenylalanine: A new serotonin‐depleting agent

The availability of a compound that appears to inhibit biosynthesis of serotonin without interfering with serotonin binding sites or with catecholamine metabolism provides a valuable new tool to explore the action of serotonin in the brain.

Abstract

This paper reports the first human trials of p‐chlorophenylalanine, which in animals has been shown to deplete brain and peripheral serotonin. In 6 normal prison inmate volunteers, a dose of 3,000 mg. per day of p‐chlorophenylalanine produced a decline in blood serotonin to 60 to 70 per cent of pretreatment levels and in urinary excretion of 5‐hydroxy‐3‐indolylacetic acid to 10 to 50 per cent. Symptoms reported by the subiects were tiredness, dizziness, nausea, uneasiness, fullness in the head, paresthesias, headache, and constipation. These generally began at the 1,000 mg. per day dose. The availability of a compound that appears to inhibit biosynthesis of serotonin without interfering with serotonin binding sites or with catecholamine metabolism provides a valuable new tool to explore the action of serotonin in the brain.