Parkinsonism-preventing activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo

Biol Pharm Bull. 2006 Jul;29(7):1401-3. doi: 10.1248/bpb.29.1401.

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.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antiparkinson Agents / pharmacology*
  • Brain / drug effects
  • Brain / metabolism*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Parkinsonian Disorders / prevention & control*
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Antiparkinson Agents
  • Dopamine Antagonists
  • Tetrahydroisoquinolines
  • 1-methyl-1,2,3,4-tetrahydroisoquinoline
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine