末梢脱炭酸酵素阻害剤投与ラットの臓器における L-Dopa 脱炭酸酵素活性とビタミンB6との関連について

吉峯 徳, 葛谷 文男, 森 邦雄, 坂本 信夫

doi:10.3143/geriatrics.15.566

In parkinsonism, L-DOPA treatment has been reported to be effective in reducing signs & symptoms. Vitamin B₆ (VB₆), however, has been reported to reduce the effect of L-DOPA, if VB₆ is given orally or parenterally. On the contrary, the peripheral L-DOPA decarboxylase inhibitors (PDI) were reported to block L-DOPA decarboxylase (AAD) activity in the peripheral organs even when VB₆ was added to them. Clinically, some literatures described that the combined treatement (L-DOPA+PDI) showed much improvement by VB₆ administration, the others indicated that the additional VB₆ to the combined therapy showed the clinial deterioration. In order to clarify the effect of VB₆ loading on the combined treatment, authors carried out the following in vitro and in vivo animal experiment. a) In vitro experiment In rat liver homogenate, the effect of VB₆ concentration on AAD was examined. As a result, there was some adverse relation between B₆ concentration and AAD. Namely, the more VB₆ concentration increased, the more the inhibition ratio of AAD was observed. b) In vivo experiment Two PDIs (MK-486 and RO4-4602) were examined in Wistar rats: One was fed with VB₆ containing diet (VB₆ (+)), the other was fed with VB₆ deficient diet (VB₆ (-)). Furthermore, VB₆ (+) was divided into two groups; a) MK-486 (or R04-4602) 50mg/kg orally. b) a)+pal-p 10mg/Kg (i. p.) and VB₆ (-) group was MK-486 (or R04-4602) 50mg/Kg orally. After 15 weeks' feeding, rats were sacrificed by decapitation. Measurement of AAD was carried out in liver, kidney, brain & small intestine. In addition to AAD, GOT & GPT in liver and kidney were also examined. As a result, PDIs blocked the AAD activity in kidney, brain & small intestine, especially in small intestine, but not in liver. In pal-p loading groups, there was the marked reduction of AAD, compared with no VB₆ loading. Almost similar results were obtained in VB₆ (-). AAD in liver, however, showed the decrease in the VB₆ (-), which was different from VB₆ (+). GOT & GPT in liver and kindey showed no remarkable changes. From the above in vitro and in vivo experiment, authors supposed that VB₆ can combine with L-DOPA (condensation) in the blood and/or organs by the increasing concentration of VB₆, and that the increasing concentration of L-DOPA induced by blocking effect of PDI would be reduced by the increasing VB₆ in the blood and/or organs. Namely, the condensation between VB₆ and L-DOPA resulted in the decrease of substrate to AAD. Authors would recommend the careful administration of VB₆ even in the combined therapy of parkinsonism.

末梢脱炭酸酵素阻害剤投与ラットの臓器における L-Dopa 脱炭酸酵素活性とビタミンB<sub>6</sub>との関連について

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