Parkinsonism-preventing activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo.
Parkinsonism-preventing activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo.
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DOI：
10.1248/bpb.29.1401
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发表时间：
2006-07
影响因子：
2
通讯作者：
K. Okuda;Y. Kotake;S. Ohta
中科院分区：
文献类型：
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作者：
K. Okuda;Y. Kotake;S. Ohta
1-甲基-1，2，3，4-四氢异喹啉（1 MeTIQ）是一种内源性帕金森病预防物质，据报道，其5-、6-和7-羟基化衍生物在体外显示出对SH-SY 5 Y人神经母细胞瘤细胞中猪毛菜醇毒性的神经保护活性。在本研究中，我们测试了这些衍生物的预防帕金森病的潜力，通过在C57 BL小鼠体内的极试验，并通过液相色谱-串联质谱法测定脑多巴胺含量。1-甲基-4-苯基-1，2，3，6-四氢异喹啉（MPTP）可诱导帕金森病，用任何1 MeTIQ衍生物预处理均可阻止其诱导。6-Hydroxy-1 MeTIQ具有最强的预防活性。MPTP处理可降低脑中多巴胺的含量，而1 MeTIQ衍生物预处理可抑制这种降低。这些羟基-1MeTIQ衍生物可能具有治疗帕金森病的潜力以及1 MeTIQ本身。
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous parkinsonism-preventing substance, and its 5-, 6-, and 7-hydroxylated derivatives are reported to show in vitro neuroprotective activity against toxicity due to salsolinol in SH-SY5Y human neuroblastoma cells. In the present study, we tested the parkinsonism-preventing potential of these derivatives by means of the pole test in C57BL mice in vivo, and measured brain dopamine contents by liquid chromatography-tandem mass spectrometry. Parkinsonism was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydroisoquinoline(MPTP), and pretreatment with any of the 1MeTIQ derivatives prevented its induction. 6-Hydroxy-1MeTIQ showed the greatest preventive activity. The amount of dopamine in the brain was reduced by MPTP treatment, and this reduction was suppressed by pretreatment with 1MeTIQ derivatives. These hydroxy-1MeTIQ derivatives may have potential for the treatment of Parkinson's disease as well as 1MeTIQ itself.