DIMETHOXYPHENYLETHYLAMINE AND TETRAHYDROPAPAVERINE ARE TOXIC TO THE NIGROSTRIATAL SYSTEM

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, dimethoxyphenylacet aldehyde; both are potent inhibitors of mitochondrial complex I. These compounds were introduced to the unilateral caudate-putamen of male S prague-Dawley rats over 7 days using a 200-mu l mini-osmotic pump. Str iatal dopamine on the injected side showed a significant decrease to 8 6% of the non-injected side after 16.55 mu mol/7 days infusion of DMPE A, and to 73% of the non-injected side after 7.90 mu mol/7 days of THP infusion; as the non-injected side dopamine also reduced in the THP-i njected rats, dopamine on the injected side was 55% of the saline cont rol. Tyrosine hydroxylase (TH)-positive nigral neurons were decreased to 76% of the non-injected side after 16.55 mu mol/7 days infusion of DMPEA and to 77% after 7.90 mu mol/7 days of THP infusion. Dimethoxyph enyl-tetrahydroisoquinoline compounds appear to be potent nigral neuro toxins. (C) 1997 Elsevier Science B.V.