L-3,4-dihydroxyphenylalanine (levodopa) lowers central nervous system S-adenosylmethionine concentrations in humans.
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.
Surtees
R
R
Department of Child Health, Institute of Child Health, London, United Kingdom.
Hyland
K
K
D000293:Adolescent; D000405:Akinetic Mutism / Q000188:drug therapy* / Q000201:enzymology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008715:Methionine / Q000134:cerebrospinal fluid; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency*; D010661:Phenylketonurias; D011736:Pyridoxine / Q000008:administration & dosage; D012436:S-Adenosylmethionine / Q000134:cerebrospinal fluid*; D013763:Tetrahydrofolates / Q000134:cerebrospinal fluid; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid
D013763:Tetrahydrofolates; D001708:Biopterins; D014443:Tyrosine; D007980:Levodopa; D012436:S-Adenosylmethionine; D008715:Methionine; D009247:NADH, NADPH Oxidoreductases; C003402:sapropterin; D011736:Pyridoxine; C005984:5-methyltetrahydrofolate; C008404:3-methoxytyrosine