Effect of dopamine, dimethoxyphenylethylamine, papaverine, and related compounds on mitochondrial respiration and complex I activity.
We report the effect of papaverine, tetrahydro-papaverine, laudanosine, dimethoxyphenylethylamine, dopamine, and its metabolites on mitochondrial respiration and activities of the enzymes in the electron transfer complexes, as mitochondrial toxins may be implicated in the etiology and the pathogenesis of Parkinson's disease. Papaverine was the most potent inhibitor of complex I and NADH-linked mitochondrial respiration among the compounds tested next to rotenone. Tetrahydropapaverine, dimethoxyphenylethylamine, and laudanosine also inhibited NADH-linked mitochondrial respiration and complex I activity in this order. Dopamine and its metabolites showed either no inhibition or only very week inhibition. Compounds with dimethoxy residues in the phenyl ring were associated with more potent inhibition of complex I than those without. Our results warrant further studies on these and some related compounds as candidate neurotoxins causing Parkinson's disease.
Morikawa
N
N
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Nakagawa-Hattori
Y
Y
Mizuno
Y
Y
D000818:Animals; D004118:Dimethoxyphenylethylamine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology*; D011048:Polarography
D004118:Dimethoxyphenylethylamine; D010208:Papaverine; D016660:NAD(P)H Dehydrogenase (Quinone); D004298:Dopamine