Ann-Kathrine Granerus

'On‐off' phenomenon in Parkinson's disease Relationship between dopa and other large neutral amino acids in plasma

Administration of a low-protein diet to parkinsonian patients with “on-off” syndromes consistently increased the total daily time of “on” states when compared with a high-protein diet. The clinical effect of the low-protein diet may be due to a marked decrease in the plasma concentration of large neutral amino acids that compete with L-dopa for carrier-mediated transport into the brain.

Decarboxylation of orally administered l-dopa in the human digestive tract

SummaryCarboxyl labelled l-dopa was administered orally and intravenously to Parkinsonian patients and control subjects. Total radioactivity was measured in the expired air, urine and plasma. The activity in plasma was also measured before and after removal of carbon dioxide-dicarbonate. After intravenous administration about four times more radioactivity was recovered in the urine than after oral administration with a roughly corresponding decrease in the recovery from expired air, whereas a considerably smaller proportion of the total radioactivity in plasma was derived from carbon dioxide-bicarbonate. It is concluded that the major fraction of the orally administered l-dopa undergoes decarboxylation in the digestive tract before reaching the general circulation. No difference was observed between the Parkinsonian and the non-Parkinsonian group.

Intestinal decarboxylation of L-Dopa in relation to dose requirement in Parkinson's disease

SummaryThe magnitude of the decarboxylation of L-Dopa in the intestinal organs was determined by a method based on oral and intravenous administration of L-3′,4′-dihydroxyphenylalanine-1-14C (carboxyl labelled L-Dopa) and analysis of the radioactivity in urine.In 11 parkinsonian patients studied under standardized conditions 74% of L-Dopa given orally as a 0.5 g tablet was decarboxylated in the intestinal organs. Thus less than 26% of the ingested L-Dopa reached the general circulation.The possibility that individual variations in the magnitude of intestinal decarboxylation might be at least partly responsible for the individual variations in the dose requirement of parkinsonian patients was tested. There was neither any correlation between dose requirement of L-Dopa and the intestinal decarboxylation nor between that dose and the plasma disappearance rate of L-Dopa.It is concluded that other factors than those responsible for the peripheral metabolism of L-Dopa determine the individual dose requirement.

Inhibition of L-Phenylalanine Absorption by L-DOPA in Patients with Parkinsonism

Summary The effect of L-DOPA treatment on the absorption, distribution, and turnover rate of L-phenylalanine have been studied in 9 patients with parkinsonism. L-DOPA, when given with L-phenylalanine, reduced the absorption rate of this amino acid. This effect was only seen when L-DOPA and L-phenylalanine were given simultaneously. L-DOPA did not affect the plasma disappearance curve of intravenously injected L-phenylalanine. The theoretical distribution volume, the distribution rate, and turnover rate of L-phenylalanine were unaffected by the L-DOPA treatment.

Phenylalanine Absorption and Metabolism in Parkinsonian Patients

Oral and intravenous L-phenylalanine loading tests were performed in 13 Parkinsonian patients and in 12 control subjects matched for age and weight. The results showed a normal intestinal absorption and a normal elimination from plasma of phenylalanine in the Parkinsonian patients.