パーキンソン病の薬物治療

Pharmacologic Treatment of Parkinson Disease

はじめに

　パーキンソン病（Parkinson disease：PD）は19世紀初頭に記載された疾患であるが，1958年に黒質ドーパミンニューロンの変性がPDの本態であることが明らかになり，L-dopaが治療に導入されたことで，PDの生命予後は著明に改善した。さらにその後多数のドーパミン受容体刺激薬（以下，アゴニスト），モノアミン酸化酵素B阻害薬（以下，MAOBI），カテコールOメチル基転移酵素阻害薬（以下，COMTI）などの薬剤が開発され，この20年の間にもPDの機能予後は著明に改善してきた。多くのエビデンスも積み重ねられ，ここ数年でも治療に対する考え方が変わってきている。本稿では，治療開始時期を含む薬物治療に対する考え方の変遷を中心に，ごく最近認可になった新しい抗PD薬，ゾニサミドについても述べたい。

Abstract

　In this paper,I have discussed a modification in the current treatment strategy for Parkinson disease (PD) and the application of a new drug,zonisamide,for the treatment of PD.　At the beginning of the 21^st century,the following views were held strongly regarding the treatment of PD (1) L-dopa may be toxic,(2) dopamine agonist may exert neuroprotective effects,(3) dopamine agonists should be used as the initial treatment for parkinsonian patients without dementia or psychosis.　However,the paradigm has now been modified to state (1) L-dopa does not accelerate disease progression,(2) no treatment modality exerts neuroprotective effects,(3) L-dopa is more effective than dopamine agonists in alleviating motor symptoms and improving the activities of daily living (ADL) score,in parkinsonian patients.　Treatment with dopamine agonist is associated with fewer motor complications than L-dopa.　Dopamine agonist therapy is associated with more frequent adverse events than L-dopa therapy,such as hallucinations and somnolence.　There is no evidence of a long-term benefit with initial dopamine agonist therapy.　Therefore,the treatment should be determined on a case-by-case basis.　Furthermore,some clinical trials have indicated that early dopaminergic support for the degenerating dopaminergic system offers significant long-term clinical benefits for parkinsoninan patients.　Zonisamide (25-50mg/day) improves motor functions and wearing-off without worsening dyskinesia in advanced cases of Parkinson disease.　Furthermore,zonisamide affects an increases in the levels of glutathione and manganese superoxide dismutase expression and,it ameliorates reduction in the number of dopaminergic neurons in mice treated with 6-hydroxydopamine (6-OHDA).　Zonisamide may exert neuroprotective effects in parkinsonian patients.