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February 1969

Drug-Induced Changes of Extracerebral Dopa Metabolism in Man

Author Affiliations

Geneva; Basle, Switzerland
From the University of Geneva (Dr. Tissot) and F. Hoffman-La Roche & Co., Ltd., Basle, Switzerland (Drs. Bartholini and Pletscher).

Arch Neurol. 1969;20(2):187-190. doi:10.1001/archneur.1969.00480080087010

IN ANIMALS, Ro 4-4602 (N1-[DL-seryl]-N2-[2,3,4-trihydroxybenzyl] -hydrazine) in doses of 5-50 mg/kg has been shown to cause a selective inhibition of decarboxylase of aromatic amino acids in extracerebral tissues. As a consequence, the drug markedly enhances the increase of dopa (3,4-dihydroxyphenylalanine) and methyldopa which occurs in the blood after intravenous and oral administration of dopa. The catecholamines and their metabolites (mainly phenolcarboxylic acids [PCA]) are, however, decreased as compared to animals treated with dopa alone. In the brain, especially in the extrapyramidal centers, the dopa-induced rise of dopamine is markedly enhanced by Ro 4-4602. This effect has been explained by an increased supply of dopa from the blood to the brain where formation of dopamine takes place since cerebral decarboxylase is not inhibited.1-3

An increase of dopamine in extrapyramidal brain centers without a major rise of catecholamines in the extracerebral organs might be of interest

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