Maruyama W, Narabayashi H, Dostert P, Naoi M
Department of Neurology, Nagoya University School of Medicine, Japan.
J Neural Transm (Vienna). 1996;103(8-9):1069-76. doi: 10.1007/BF01291791.
N-Methyl(R)salsolinol, an endogenous neurotoxin, has been proposed to be closely involved in the pathogenesis of Parkinson's disease. The selective toxicity to dopaminergic neurons was strictly limited for (R)-enantiomer of N-methylsalsolinol. Its precursor, (R)salsolinol was enzymatically synthesized from dopamine and acetaldehyde in human. However, it has never been examined whether a non-enzymatic reaction produces racemic salsolinol derivatives from dopamine especially in patients under L-DOPA therapy. To clarify the point, their contents were examined in intraventricular fluid from parkinsonian patients administrated with L-DOPA. Only (R)-enantiomer of N-methylsalsolinol and very low concentration of salsolinol could be detected. The results suggest that N-methyl(R)salsolinol synthesis may not depend on dopamine level, but on the activity of enzymes related to its synthesis and/or catabolism. The results are discussed in relation to pathogenesis Parkinson's disease.
N-甲基（R）-salsolinol是一种内源性神经毒素，被认为与帕金森病的发病机制密切相关。N-甲基salsolinol的（R）-对映体对多巴胺能神经元的选择性毒性受到严格限制。它的前体（R）-salsolinol是由人体中的多巴胺和乙醛通过酶促合成的。然而，从未研究过非酶促反应是否会从多巴胺中产生外消旋salsolinol衍生物，特别是在接受左旋多巴治疗的患者中。为了阐明这一点，对接受左旋多巴治疗的帕金森病患者脑室内液中的这些物质含量进行了检测。仅检测到N-甲基（R）-salsolinol的（R）-对映体和极低浓度的salsolinol。结果表明，N-甲基（R）-salsolinol的合成可能不依赖于多巴胺水平，而是取决于与其合成和/或分解代谢相关的酶的活性。结合帕金森病的发病机制对结果进行了讨论。
