長期間L-Dopa大量内服パーキンソン氏病例における末梢Dopa脱炭酸阻害剤の併用

ON THE EFFECT OF DOPA DECARBOXYLASE INHIBITOR FOR THE PARKINSON'S DISEASE PATIENTS TREATED BY L-DOPA FOR LONG TERM

I．はじめに

　現今，L-Dopaの慎重な経口大量投与がパーキンソン氏病に対する有効な治療法であることが広く認められている。しかしL-Dopaの内服量がきわめて大量であるとともに長期間内服例が増加するにつれて適正維持量を内服しているにもかかわらず効果が不満足になる例，日内変動やOn＆Off現象を呈する例，数年間にわたり服用していたにもかかわらず胃腸系をはじめとする各種副作用が発現し対策に苦慮する例が見られるようになつている。著者は昭和44年11月以来L-Dopa内服治療法を70余例の症例に行なつてきているが内服開始後3年では78.4％の症例が効果に変化を生じ投与量の調整を必要とし，内服開始後4年では87.2％の症例に副作用または効果の変化を生じL-Dopa投与量の調整や他薬剤の投与など効果安定と副作用解除のための対策を行なわねばならない現状である。

　投与L-Dopaの体内代謝については多くの研究が行なわれ投与L-Dopaの95％以上は腸管，腎，肝，血管内皮細胞など脳髄以外の末梢組織に存在するDopa脱炭酸酵素の作用によつてDopamineに変化され脳髄内に入ることが阻止されるためL-Dopaの型で血液脳関門を通過して脳内にとりこまれる量が極めて少ないことが知られる様になつた^30）。これによつてL-Dopaを大量に内服する必要のあつた原因が明らかになるとともにL-Dopa内服による副作用が末梢組織におけるDopa—mineの過剰産生に原因する可能性を示唆した。この様な研究知見から末梢組織におけるL-Dopaの脱炭酸を阻害することによつて，より多量のL-Dopaを血液脳関門を通過させて中枢活性物質を産生させる必要があると考えられるようになり，L-DopaとDopa脱炭酸阻害剤の併用療法が注目されてきている。

The author have had the oppotunity to handle 70 patients suffering from Parkinson's disease with L-dopa. In these therapeutic experiences, the author faced with decreased therapeutic effect of L-dopa, daily fluctuation of therapeutic effect, "On and Off" phenomena and side effect and the regu-lation of L-dopa dosis has no effect for all of these long term L-dopa syndrome.

The author have had the experiences of treat-ment by L-dopa associated with MK-486 for their long term L-dopa syndrome. This study reports the results of combined therpy in 6 Parkinson's disease patients. These patients had been treated by L-dopa for 32 months in average and were divided into three groups ; two patients are that the effect of L-dopa decreased recently beside some side effect which were uncontrollable by regulation of dosis of L-dopa, two patients are that the strong fluctuation of the effect of L-dopa for Parkinson's syndrome and "On and Off" phenomena appeared daily beside some side effect and the other two patients are that some side effect such as gastro-intestinal disorder and psychiatric disorder appeared.

The tablet containing L-dopa and MK-486 in fixed ratio (10 : 1) were given by adaptated with L-dopa dosis that was given before new treatment.

The long term L-dopa syndrome as described above disappeared by combined therapy and theoriginal effect of L-dopa reappeared to the same level with most effective score of symptom, sign and functional disability which was observed in the early stage of L-dopa therapy. The severity and daily frequency of "On and Off" phenomena decreased gradually also. The gastrointestinal side effect disappeared immediately after change to combined therapy. Headache and psychiatric dis-order such as depression and hallucination also dis-appeared by change to combined therapy. On the other hand, hypotension due to L-dopa therapy continued even by combined therapy and hypo-tension is still important side effect in combined therapy.

The advantage of combined therapy with L-dopa and MK-486 are as follows.

(1) The dosis of L-dopa necessary to obtain a similar clinical effect with L-dopa alone reduced to 1/5.

(2) The peripheral side effect by L-dopa dis-appeared, particularly gastrointestinal side effect.

(3) The central side effect such as psychiatric disorder reduced.

(4) The unstable effect such daily fluctuation of L-dopa effect and "On and Off" phenomena dis-appeared and the effect of L-dopa became stable.