Neurotoxic effects of papaverine, tetrahydropapaverine and dimethoxyphenylethylamine on dopaminergic neurons in ventral mesencephalic-striatal co-culture.
We report neurotoxic effects of papaverine, tetrahydropapaverine, dimethoxyphenylethylamine (DMPEA), and 1-methyl-4-phenylpyridinium ion (MPP+) on dopaminergic neurons in ventral mesencephalic-striatal co-culture. These compounds have been reported as mitochondrial toxins which may be implicated in the etiology and pathogenesis of Parkinson's disease. Tyrosine hydroxylase (TH)-positive neurons were decreased in dose-dependent manner by these compounds. Papaverine and MPP+ were most toxic to TH-positive neurons among the compounds tested. The order of the toxicity on TH-positive neurons was papaverine, MPP+, tetrahydropapaverine and then DMPEA. This order of toxicity was approximately the same as that reported on the inhibitory effect of these compounds on NADH-linked mitochondrial respiration and complex I activity. These findings indicate that the presence of dimethoxy residues in the catechol ring augments toxicity to dopaminergic neurons in culture.
Goto
K
K
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Mochizuki
H
H
Hattori
T
T
Nakamura
N
N
Mizuno
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D015415:Biomarkers; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology*; D004118:Dimethoxyphenylethylamine / Q000633:toxicity*; D004622:Embryo, Mammalian; D007546:Isoquinolines / Q000633:toxicity*; D008636:Mesencephalon / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009498:Neurotoxins; D010208:Papaverine / Q000633:toxicity*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D004118:Dimethoxyphenylethylamine; D007546:Isoquinolines; D009498:Neurotoxins; C063395:tetrahydropapaverine; D010208:Papaverine; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium