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Article
December 24, 1997

Brain Serotonin Neurotoxicity and Fenfluramine and Dexfenfluramine

Author Affiliations

Good Calorie Products Mill Valley, Calif

JAMA. 1997;278(24):2141. doi:10.1001/jama.1997.03550240031020
Abstract

To the Editor.  —Recently the serotonin-enhancing diet drugs, fenfluramine and dexfenfluramine, were withdrawn from the market in the United States. These drugs appear to deplete the brain of serotonin, suggesting that normal physiology during treatment may require constant replenishment of serotonin.1 Brain serotonin is synthesized from tryptophan. The rate-limiting step in brain serotonin synthesis is entry of tryptophan into the brain. Such entry is proportionate to the ratio of plasma tryptophan to other large neutral amino acids (Trp/ LNNA) that compete with tryptophan for passage past the blood-brain barrier. A higher Trp/LAA ratio corresponds to a greater capacity to synthesize brain serotonin.In women, but not in men, dieting has been repeatedly demonstrated to decrease plasma tryptophan levels and Trp/ LNAA ratios by Cowen and colleagues (see reference for citations).2 Four other laboratories have confirmed lower Trp/ LNAA ratios in dieting women.3-6Long-term dexfenfluramine treatment is accompanied

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