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

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.

• Authors: Katsuhiro Okuda, Yaichiro Kotake, Shigeru Ohta
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 29 Issue 7 Pg. 1401-3 (Jul 2006) ISSN: 0918-6158 [Print] Japan
• PMID: 16819177 (Publication Type: Journal Article)

Chemical References

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

Topics

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