パーキンソン病に対するL-DOPA治療と脱炭酸酵素阻害剤（塩酸Benserazide）併用治療—第Ⅰ報：臨床知見について

COMPARATIVE STUDIES OF L-DOPA ALONE AND COMBINATION WITH A PERIPHERAL DOPA DECARBOXYLASE INHIBITOR, HCL-BENSERAZIDE, ON PARKINSON'S DISEASE : PART I: CLINICAL ASPECTS

Ⅰ．はじめに

　パーキンソン病に対して線条体のドーパミン欠乏を補う目的でL-DOPA治療が確立されたが，経口投与されたL-DOPAは，消化管や腎臓などの末梢における脱炭酸酵素により分解代謝されてしまうため血液脳関門を通過しえず，90％以上が脳実質に対しては無効となる^1,2）。このためパーキンソン病治療には，L-DOPAの大量投与を余儀なくされている。

　ところが1966年Udenfriend^3）により，DOPA脱炭酸酵素阻害剤（MK−486）を併用投与することにより，L-DOPAの単独投与にくらべてguinea pigの脳内のcatecholamineを有意に増加させることが発見され，Cotziasら^4,5）により臨床応用もはじめられた。

The L-DOPA treatment with DOPA de-carboxylase inhibitor permits a reduction in DOPA dosage and in some peripheral side effects inParkinson's disease. We have started one of these drugs, MADOPAR (L-DOPA 100 mg and bensera-zide 25 mg in every capsule) on 1974. The present paper aims to analyse our own clinical experience with L-DOPA treatment or MADOPAR treatment. Either treatment were done for the same groupe of 25 patients with paralysis agitans, 9 men and 16 women. The age of these patients was 61.8+ 8. 8 year old, course of illness being 7. 4+4.4 years and duration of MADOPAR treatment was 13.5+ 6. 9 months.

1) The mean maintenance dose of L-DOPA was 2100+700 mg/day in L-DOPA alone treatment and 418+173 mg/day in MADOPAR treatment. From this finding, the effect of MADOPAR is culculated five times of that of L-DOPA alone.

2) The clinical effects of the treatment with MADOPAR was superior to the treatment with L-DOPA alone on many symptoms. Score of rigidity and tremor showed better in rate of im-provement, akinesisa and disturbance of ADL showed the second improvement, and Yahr's score did not show the significant change on both regimens.

3) Adverse effects : Thirty two percent of patients L-DOPA groupe complained nausea, which was only eight percent MADOPAR groupe. The blood pressure did not change significantly on either groupe. The slight oscillation of symptoms in daytime was observed in only two cases in either groupe. The involuntary movement (induced by L-DOPA) increased to thirty six percent by MADOPAR as compare with twelve percent by L-DOPA alone. The dosage of MADOPAR in patients presenting involuntary movement was not always so high as for maintenance dosage. It is therefore considered that the dyskinesia may be due to the susceptibility of each indivisual patient to medicine, rather than its dosage.

4) GUR (Global Utility Rating), that takes the concideration of clinical effects and adverse effects, was superior for MADOPAR in thirteen cases to L-DOPA. Eight cases showed equal effects on either therapy and other four cases was inferior on MADOPAR therapy.

5) The comparison of clinical effects between MADOPAR and the combination therapy with L-DOPA and MK-486 was investigated in the preve-ous reports.