Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
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Parkinsonism-Preventing Activity of 1-Methyl-1,2,3,4-tetrahydroisoquinoline Derivatives in C57BL Mouse in Vivo
Katsuhiro OkudaYaichiro KotakeShigeru Ohta
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2006 Volume 29 Issue 7 Pages 1401-1403

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Abstract

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.

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© 2006 The Pharmaceutical Society of Japan
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