Löschmann P A, Lange K W, Kunow M, Rettig K J, Jähnig P, Honoré T, Turski L, Wachtel H, Jenner P, Marsden C D
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, United Kingdom.
J Neural Transm Park Dis Dement Sect. 1991;3(3):203-13. doi: 10.1007/BF02259538.
Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPA-antagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.
帕金森病中多巴胺能黑质纹状体神经元的退化导致从丘脑底核到基底神经节输出核的兴奋性谷氨酸能投射过度活跃，从而导致僵硬和运动不能。理论上，对这些过度活跃系统的药物阻断应能改善帕金森病症状。选择性AMPA拮抗剂NBQX和竞争性NMDA拮抗剂CPP单独给药时在帕金森病动物模型中无效，但与阈剂量的左旋多巴联合给药时可改善帕金森病症状并刺激运动活性。在MPTP处理的（1-甲基-4-苯基-1,2,3,6-四氢吡啶）普通狨猴和单侧黑质6-羟基多巴胺（6-OHDA）损伤的大鼠中可见这些协同效应。因此，竞争性NMDA和非NMDA拮抗剂可能为帕金森病的治疗提供一种新的治疗策略。
