Long-Term Therapy of Myoclonus and Other Neurologic Disorders with L-5-Hydroxytryptophan and Carbidopa

Melvin H. Van Woert, David Rosenbaum, John Howieson, Malcolm B. Bowers

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

We evaluated the therapeutic effect of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin (5-hydroxytryptamine), combined with carbidopa, a peripheral decarboxylase inhibitor, in patients with intention myoclonus and examined the serotonin metabolites in spinal fluid, blood and urine before and during therapy. In 18 patients with intention myoclonus due to anoxia or other brain damage, 11 derived more than 50 per cent overall improvement during treatment with L-5HTP and carbidopa. Spinal-fluid 5-hydroxyindoleacetic acid was 35 per cent lower in patients with intention myoclonus than in controls (P<0.05). Therapy with L-5HTP and carbidopa increased the concentration of serotonin metabolites in urine and spinal fluid. We postulate that a deficiency of brain serotonin is causally related to intention myoclonus and that the therapeutic effect of L-5HTP and carbidopa may be due to the repletion of serotonin in regions of the brain where serotoninergic neurons have degenerated. (N Engl J Med 296:70–75, 1977) There have been several clinical investigations demonstrating the effectiveness of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin (5-hydroxytryptamine), in combination with carbidopa, an extracerebral decarboxylase inhibitor, for the therapy of post-anoxic intention myoclonus.1 2 3 As shown in Figure 1, serotonin is formed from the essential amino acid tryptophan by, first, its hydroxylation to L-5HTP and then decarboxylation of L-5HTP to serotonin. The peripheral L-aromatic amino acid decarboxylase inhibitor, carbidopa, prevents the conversion of L-5HTP to serotonin outside the brain and thereby increases serotonin synthesis from L-5HTP in the central nervous system while at the same time decreasing the pharmacologic effects of serotonin in.

Original languageEnglish
Pages (from-to)70-75
Number of pages6
JournalNew England Journal of Medicine
Volume296
Issue number2
DOIs
StatePublished - 13 Jan 1977

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