ParkinsonismにおけるMK−486単独投与の効果—臨床症状と血液，尿，髄液中カテコールアミンの検討

THE EFFECT OF MK-486 ALONE ON PARKINSONISM:STUDIES ON CLINICAL SYMPTOMS AND CHANGES OF CATECHOLAMINE CONCENTRATIONS IN THE BLOOD, URINE, AND CEREBROSPINAL FLUID

I．はじめに

　L-hydrazinomethyldopa （MK-486）は，脳以外の末梢部でL-DOPA decarboxylaseを抑制する作用を有する。したがつてL-DOPAと併用することにより，L-DOPA単独投与の場合よりもより少量のL-DOPAで血中DOPA濃度を高く維持し脳内アミンを高めるため，Parkinsonismの治療に有用であることが臨床的に確認されている^{3,7-9,13,27,29,30,32-34,37,38,43,48）}。しかもMK−486は動物にも人体にも特に副作用は認められていない（Jaffe,1973^27）。　Rao　＆　Calne,1973^43））。

　しかし，MK−486を実際に臨床的に使用するにあたつては，L-DOPAとの併用による場合だけでなく，MK-486それ自身が単独で，脳のカテコールアミン代謝にどのような影響を及ぼすかについて充分検討しておくことも必要であろう。MK−486単独を投与した場合の効果については，臨床的になんら見るべき変化がなかつたとする簡単な記載がみられるが（Lotti,1973^32），　Marsden，1973^34）），それ以上に詳しく検討した報告はないようである。

　この報告の目的は，Parkinsonismの臨床症状，血中，尿中，髄液中のカテコールアミン及びその代謝産物にMK-486がどのような影響を与えるかについて検討することにある。

The purpose of this paper is to report the effect of MK-486 alone on the clinical symptoms of Parkinsonism, and on the concentrations of catecholamines and their metabolites in the blood, urine, and cerebrospinal fluid. The materials con-sisted of 14 cases with Parkinsonism, ranging from 60 to 87 years of age. In patients who had received L-dopa, trihexyphenidil hydrochloride, phenothia-zines, or reserpine, or combinations of these, the drugs were discontinued for one week before the study. The results were as follows.

1) In 2 cases MK-486 was administered alone at the dose of 60 mg for 3 days and then 150 mg for 3 days, and compared with 2 cases administered placebo. There was no appreciable effect on the clinical symptoms of Parkinsonism. After MK-486, only a trace of DOPA and dopamine was detectable in the blood. Changes in the urinary concentrations of DOPA, dopamine, and HVA showed no re-markable tendency.

2) In 10 cases MK-486 was administered alone 75 mg for 3 days and then 150 mg for 4 days. There was no improvement in the symptoms of Parkinsonism. Measurements of catecholamines in the cerebrospinal fluid revealed that 6 showed an increase of DOPA, 5 showed an increase of dopamine, while in 8 cases HVA was decreased. Following combined administration of MK-486 and L-dopa at the dose of 60 mg and 750 mg respectively for one week, all cases showed an increase of DOPA and 7 cases showed an increase of dopamine and HVA in the cerebrospinal fluid.

It was concluded that administration of MK-486 alone was ineffective in the treatment of Parkinsonism.

The reasons for the discrepancy between the lack of improvement in the clinical symptoms and the elevation of CSF catecholamines following admin-istration of MK-486 alone were discussed.