1. Academic Validation
  2. Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system

Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system

  • Brain Res. 1997 Oct 31;773(1-2):108-16. doi: 10.1016/s0006-8993(97)00922-0.
I Koshimura 1 H Imai T Hidano K Endo H Mochizuki T Kondo Y Mizuno
Affiliations

Affiliation

  • 1 Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. ikoshi@med.juntendo.ac.jp
Abstract

We report the toxic effects of 3,4-dimethoxyphenylethylamine (DMPEA), and tetrahydropapaverine (THP) on the rat nigrostriatal system; THP is a tetrahydroisoquinoline compound which may be derived from DMPEA by conjugation of DMPEA and its oxidative metabolite, dimethoxyphenylacetaldehyde; both are potent inhibitors of mitochondrial complex I. These compounds were introduced to the unilateral caudate-putamen of male Sprague-Dawley rats over 7 days using a 200-microl mini-osmotic pump. Striatal dopamine on the injected side showed a significant decrease to 86% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA, and to 73% of the non-injected side after 7.90 micromol/7 days of THP infusion; as the non-injected side dopamine also reduced in the THP-injected rats, dopamine on the injected side was 55% of the saline control. Tyrosine hydroxylase (TH)-positive nigral neurons were decreased to 76% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA and to 77% after 7.90 micromol/7 days of THP infusion. Dimethoxyphenyl-tetrahydroisoquinoline compounds appear to be potent nigral neurotoxins.

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