The neurochemistry of Parkinson's disease: effect of L-dopa therapy.
Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as "good responders" as compared to "poor responders." Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum.
D000368:Aged; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008750:Methyldopa / Q000378:metabolism; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D007980:Levodopa; D008750:Methyldopa; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004296:Dopa Decarboxylase; D004298:Dopamine; D006719:Homovanillic Acid