NIACIN DEPLETION IN PARKINSONIAN PATIENTS TREATED WITH L-DOPA, BENSERAZIDE AND CARBIDOPA
NIACIN DEPLETION IN PARKINSONIAN PATIENTS TREATED WITH L-DOPA, BENSERAZIDE AND CARBIDOPA
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DOI：
10.1042/cs0560089
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发表时间：
1979-01-01
期刊：
影响因子：
--
通讯作者：
LEES, AJ
中科院分区：
文献类型：
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作者：
BENDER, DA;EARL, CJ;LEES, AJ
苯丝肼和卡比多巴是用于治疗帕金森S病的脱羧酶抑制剂，它们抑制大鼠和小鼠肝脏的犬尿氨酸水解酶，导致色氨酸合成烟酰胺辅酶减少，并增加对饮食烟酸的依赖。可能是由于抑制烟酰胺核苷酸的内源性合成而导致的，但在接受这两种药物治疗的患者中还没有报道。在接受多巴单独治疗或与外周多巴脱羧酶抑制剂联合治疗的患者中，尿中N1-甲基烟酰胺的排泄减少到控制值的40%。N1-甲基烟酰胺是烟酰胺核苷酸代谢的产物。这些患者中的许多人可以被归类为烟酸缺乏的风险，即使不是坦率地说缺乏。接受多巴加脱羧酶抑制剂治疗的患者，而不是单用多巴治疗的患者，表现出黄原酸排泄减少，犬尿氨酸排泄增加，这在犬尿氨酸途径被抑制后是预期的，可能表明边缘维生素B6缺乏。
Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson''s disease, inhibit the enzyme kynurenine hydrolase in rat and mouse liver, causing reduced synthesis of nicotinamide coenzymes from tryptophan, and an increased reliance on dietary niacin. Pellagra might be expected as a result of the inhibitin of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug. The urinary excretion of N1-methyl-nicotinamide, a product of nicotinamide nucleotide metabolism, is reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. Many of these patients could be classified as at risk of niacin deficiency, even if not frankly deficient. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.