Two groups of 6 patients with Parkinson's disease were treated: (Group A) with L-DOPA for 65 days, or (Group B) with L-DOPA+Ro 4-4602 for 30 days. At stated intervals, both groups underwent clinical evaluation, lumbar puncture and measurement of L-DOPA in plasma. A significant improvement in total disability (Webster scale) and akinesia was observed in both groups, but rigidity was improved only in Group B. HVA in CSF increased from its low basal value much more in Group A than in B; 5-HIAA did not change. L-DOPA curves in plasma were similar in the two groups. Baseline Webster scale and akinesia were inversely correlated with basal HVA in all 12 patients. Basal HVA was also inversely correlated with the same clinical parameters evaluated at the end of the trial in all patients. Furthermore, L-DOPA peaks were directly related to CSF HVA level and to improvement (W. R. S. and akinesia) only in patients receiving the combined treatment (Group B). It was concluded that in parkinsonian syndromes clinical improvement was inversely related to severity of the illness and basal HVA in CSF, independent of the type of treatment; treatment with L-DOPA+Ro 4-4602 gave better clinical results than L-DOPA alone, and it restored CSF HVA to a more normal level; the combination with Ro 4-4602 made it possible to administer only one fifth of the quantity of L-DOPA and still to obtain the same L-DOPA level in plasma with better clinical results; and, in patients treated with L-DOPA+Ro 4-4602, the L-DOPA plasma peak was directly related to CSF HVA, Webster scale and akinesia. This means that, once peripheral decarboxylation of L-DOPA has been abolished, plasma levels are very important for L-DOPA availability in the brain.
- DOPA decarboxylase inhibitor
- Ro 4-4602
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology (medical)