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, 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.
Koshimura
I
I
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. ikoshi@med.juntendo.ac.jp
Imai
H
H
Hidano
T
T
Endo
K
K
Mochizuki
H
H
Kondo
T
T
Mizuno
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004118:Dimethoxyphenylethylamine / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D007546:Isoquinolines / Q000633:toxicity*; D008297:Male; D009498:Neurotoxins; D011699:Putamen / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004118:Dimethoxyphenylethylamine; D007546:Isoquinolines; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; C063395:tetrahydropapaverine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine