パーキンソニズムのL-dopa療法におけるpyridoxine投与の臨床的意義

CLINICAL SIGNIFICANCE OF PYRIDOXINE ADMINISTRATION IN L-DOPA THERAPY OF PARKINSONISM

I．はじめに

　パーキンソン病のL-dopa療法において，末梢性脱炭酸酵素抑制剤を含まないL-dopaの単剤投与の場合には，pyridoxine （pr vitamine B_6）の同時投与で，L—dopaの臨床効果が容易に相殺されてしまうことは周知の事実である。ところが最近では，L-dopaにMK 486（L-methyldopa hydrazine）あるいはR₀4-4602（塩酸benserazide）などの末梢性脱炭酸酵素抑制剤（DI）を併用し，末梢（脳外）におけるdopaのdopamine （DA）への代謝を抑制することにより，より少量のdopa量で良好な臨床成績が得られるようになつた。

　ところでわれわれはすでに，このようなL-dopaとDI併用の場合には，prの追加投与で，L-dopaの単剤投与の場合におけるような臨床的なadverse effectはみられず，かえつて脳内DA濃度を上昇させるのではないかと考えられることについて実験的，臨床的に考察を加えて報告したが^16,17），このたびはさらに多数の臨床例で同様の検討を加えると同時に，pr投与前後における髄液中5—Hydroxyindole acetic acid （5—HIAA）の濃度を測定し，その変動の臨床的意義についても考察を加え報告する。

22 patients of idiopathic parkinsonism were analyzed to investigate the effect of concomitant pyridoxine administration to the patients who had been taking L-dopa in combination with peripheral decarboxy lase inhibitor (MK486, L-dopa/MK486: L/M). 5-HIAA concentrations in the CSF were also measured before and after the administration of daily 60-240mg pyridoxine during three weeks. On the other hand, supplemental experiments were performed to confirm the clinical observations.

Results 1. Administration of pyridoxine evoked oral dyskinesias and dyskinesias on the extremities in two patients. In three patients, pyridoxine prevented from the aggravation of the clinical symptoms of parkinsonism which might be retional-ly anticipated by decreasing the amount of L/M administrations. After all it was confirmed that pyridoxine increased the effect of L/M in at least six of eighteen patients who took pyridoxine con-comitantly with L/M.

2. The dopamine (DA) concentrations of the brains after L-dopa injections with MK486 showed by 30% higher levels in the rats which had received the pretreatment by consecutive 2 weeks of daily 25mg/kg pyridoxine injections than in the those without such pretreatment.

3. Lumbar CSF 5-HIAA concentration was 21.6±8.9ng/ml in the non-parkinsonian control group. CSF 5-HIAA concentrations of the patients who had been taking L/M continuously were lower than the control value. Addition of pyridoxine to L/M elevated the 5-HIAA concentrations in eight of the nine patients.

Conclusion 1. It was confirmed from the clinical and experimental studies that the addition of pyridoxine elevated the intracerebral DA con-centration when administered to the patients who had been taking L-dopa with peripheral de-carboxylase inhibitor. 2. From the fact that pyridoxine elevated the CSF 5-HIAA concentration, it was speculated that pyridoxine might increase the intracerebral serotonin concentration in the L/M therapy of parkinsonism.