Letter | Published:

Transamination is a Major Pathway of L-Dopa Metabolism following Peripheral Decarboxylase Inhibition

Naturevolume 247pages364366 (1974) | Download Citation

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Abstract

WHEN L-3,4-dihydroxyphenylalanine (L-dopa) is administered to human subjects1, the greater proportion is metabolised by decarboxylation, a small amount by O-methylation and traces only by transamination2. It seems likely that the benefit resulting from L-dopa therapy in Parkinsonian patients derives largely from the generation of one of its metabolites, dopamine, by decarboxylation within the central nervous system3. Less than 5% of administered L-dopa becomes available for this purpose: most of the dose is decarboxylated peripherally4. There is good reason to believe that the dopamine so formed is unable to penetrate the blood-brain barrier to any great extent5, so that little of the original dose is available to contribute to the therapeutic response. By blocking peripheral decarboxylase, however, certain decarboxylase inhibitors6,7, which are themselves unable to cross the blood-brain barrier to any significant extent8, bring about an accumulation in the plasma of administered L-dopa, thus providing a higher concentration gradient to enter the central nervous system and allowing lower oral doses of L-dopa to be employed therapeutically9.

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Affiliations

  1. Bernhard Baron Memorial Research Laboratories, and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, W6 0XG

    • M. SANDLER
    • , R. D. JOHNSON
    •  & C. R. J. RUTHVEN
  2. Department of Medicine, Royal Postgraduate Medical School, London, W12 0HS

    • J. L. REID
    •  & D. B. CALNE

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https://doi.org/10.1038/247364b0

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