Treatment of Parkinson's disease with l-DOPA and decarboxylase inhibitor

Summary Clinical trials on the effect of l-DOPA and decarboxylase inhibitor, Ro 4-4602, in the long-term treatment of Parkinson's disease were carried out and compared with l-DOPA alone. Altogether 59 parkinsonian patietns were treated for 3 to 9 months. For correlative studies the plasma level of DOPA and the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) was analysed.A daily dosage of 800 to 1000 mg of l-DOPA combined with 200 to 250 mg of decarboxylase inhibitor induced during long-term treatment a significant therapeutic response which was equal to that induced by 4 to 5 g of l-DOPA alone. During combined treatment there was a significant reduction of nausea and especially of vomiting. However, in the dosage range used the frequency of abnormal involuntary movements was equal to that with l-DOPA alone.There were only a few transient laboratory abnormalities during l-DOPA and decarboxylase inhibitor treatment. Liver biopsy studies on 10 volunteer parkinsonian patients did not show any light or electron microscopic changes which could be related to the treatment.The maximum plasma level of l-DOPA after 200 mg of l-DOPA and 50 mg of Ro 4-4602 was equal to that of 1000 mg of l-DOPA alone.During l-DOPA and decarboxylase inhibitor treatment the concentration of HVA in the CSF increased significantly and correlated significantly with the dosage but not with the degree of clinical improvement. On the other hand, the concentration of 5-HIAA in the CSF decreased significantly during treatment. l-DOPA and decarboxylase inhibitor seems to be an effective, well-tolerated and safe drug in the treatment of parkinsonian patients. The decrease in gastro-intestinal side-effects affords a considerable advantage over l-DOPA alone.Supported by a grant from the Signe and Ane Gyllenberg's Foundation.