L-3,4-dihydroxyphenylalanine (levodopa) lowers central nervous system S-adenosylmethionine concentrations in humans

J Neurol Neurosurg Psychiatry. 1990 Jul;53(7):569-72. doi: 10.1136/jnnp.53.7.569.


To determine whether levodopa reduces the levels of S-adenosylmethionine in the human central nervous system, cerebrospinal fluid (CSF) concentrations of S-adenosylmethionine, methionine, 3-methoxytyrosine, levodopa and 5-methyltetrahydrofolate were measured in six children with dopamine deficiency before and after treatment. In four, the lack of dopamine was secondary to a reduction in concentration of levodopa and these were treated with levodopa together with a peripheral dopa-decarboxylase inhibitor. In the other two, levodopa in the central nervous system naturally accumulated due to a congenital deficiency of aromatic-L-amino acid decarboxylase and these were treated with pyridoxine (which in this condition lowers central levodopa concentrations). Raising levodopa concentrations in the central nervous system caused a fall in CSF S-adenosyl-methionine concentration and a rise in CSF 3-methoxytyrosine concentration. No change was observed in CSF methionine concentration and in all patients CSF 5-methyltetrahydrofolate concentration was normal. With one exclusion there was a linear relationship between CSF S-adenosylmethionine and 3-methoxytyrosine concentrations. This is the first demonstration of such effects in humans and the implications upon levodopa therapy are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Akinetic Mutism / drug therapy*
  • Akinetic Mutism / enzymology
  • Biopterin / analogs & derivatives*
  • Biopterin / deficiency
  • Child, Preschool
  • Humans
  • Infant
  • Levodopa / administration & dosage*
  • Levodopa / pharmacokinetics
  • Methionine / cerebrospinal fluid
  • NADH, NADPH Oxidoreductases / deficiency*
  • Phenylketonurias*
  • Pyridoxine / administration & dosage
  • S-Adenosylmethionine / cerebrospinal fluid*
  • Tetrahydrofolates / cerebrospinal fluid
  • Tyrosine / analogs & derivatives*
  • Tyrosine / cerebrospinal fluid


  • Tetrahydrofolates
  • Biopterin
  • Tyrosine
  • Levodopa
  • S-Adenosylmethionine
  • Methionine
  • NADH, NADPH Oxidoreductases
  • sapropterin
  • Pyridoxine
  • 5-methyltetrahydrofolate
  • 3-methoxytyrosine