Lange K W, Riederer P
Laboratory of Clinical Neurochemistry, University of Würzburg, Germany.
Life Sci. 1994;55(25-26):2067-75. doi: 10.1016/0024-3205(94)00387-4.
Recent findings in monkeys indicate that excitatory amino acids such as glutamate are involved in the pathophysiological cascade of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)- induced neuronal cell death. The neuroprotective effects of competitive and non-competitive NMDA (N-methyl-D-aspartate) antagonists against MPTP toxicity support the hypothesis that NMDA receptor-mediated events are involved in the neurotoxicity of MPTP. These results suggest that the clinical trial of NMDA antagonists in patients with Parkinson's disease should be performed. Further evidence obtained in animal models of Parkinson's disease indicates that both competitive NMDA antagonists and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) antagonists show symptomatic anti-parkinsonian activity in combination with L-DOPA. Glutamate antagonists may therefore retard the progression and improve the symptomatology of Parkinson's disease. The 1-amino-adamantanes amantadine and memantine have recently been shown to be non-competitive NMDA antagonists and are widely used in Europe as anti-parkinsonian agents. Both compounds are likely to cause pharmacotoxic psychosis as an unwanted side-effect. Clinical trials are needed to test the efficacy of the 1-amino-adamantanes with respect to the progression of Parkinson's disease.
近期在猴子身上的研究结果表明，诸如谷氨酸等兴奋性氨基酸参与了MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）诱导的神经元细胞死亡的病理生理级联反应。竞争性和非竞争性NMDA（N-甲基-D-天冬氨酸）拮抗剂对MPTP毒性的神经保护作用支持了这样一种假说，即NMDA受体介导的事件参与了MPTP的神经毒性。这些结果表明，应该对帕金森病患者进行NMDA拮抗剂的临床试验。在帕金森病动物模型中获得的进一步证据表明，竞争性NMDA拮抗剂和AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）拮抗剂与左旋多巴联合使用时均显示出有症状的抗帕金森病活性。因此，谷氨酸拮抗剂可能会延缓帕金森病的进展并改善其症状。1-氨基金刚烷类药物金刚烷胺和美金刚最近被证明是非竞争性NMDA拮抗剂，并在欧洲被广泛用作抗帕金森病药物。这两种化合物都可能会引起药物毒性精神病这一不良副作用。需要进行临床试验来测试1-氨基金刚烷类药物对帕金森病进展的疗效。
