Archer T, Palomo T, Fredriksson A
Department of Psychology, University of Göteborg, Göteborg, Sweden.
Amino Acids. 2002;23(1-3):71-85. doi: 10.1007/s00726-001-0112-8.
Several compounds with antagonistic actions on N-methyl-D-aspartate (NMDA) receptors were tested for an antiakinesic action in hypoactive MPTP-treated C57 BL/6 mice rendered tolerant to the motor activity enhancing effects of the 20 mg/kg, s.c., dose of L-Dopa; each compound was administered 60 min before the administration of the dopamine precursor. The classes of compounds studied included the noncompetitive NMDA antagonists, memantine, amantadine and MK-801, the competitive NMDA antagonist, CGP 40116, the anticonvulsive and putative anticonvulsive agents, lamotrigine and FCE 26743, with a partial glutamatergic antagonistic action. All six compounds elevated locomotor, rearing and total activity counts of L-Dopa-tolerant mice in co-administration with L-Dopa in dose-specific or dose-dependent manners but only memantine and MK-801 affected motor activity in the control mice, that also received chronic L-Dopa treatment. Thus, the restorative actions of those compounds in suprathreshold L-Dopa-tolerant MPTP-treated mice subjected to "wearing-off" of L-Dopa efficacy were assessed in a series of experiments. Within each class of potentially therapeutic agents a differential restorative efficacy of the motor activity-stimulating effects of hypoactive MPTP mice was obtained, confirming the putative antiparkinsonian applications of compounds with glutamate antagonistic actions.
对几种对N-甲基-D-天冬氨酸（NMDA）受体有拮抗作用的化合物进行了测试，以观察其对经MPTP处理而活动减少的C57 BL/6小鼠的抗运动不能作用，这些小鼠对20 mg/kg皮下注射剂量的左旋多巴的运动活性增强作用产生了耐受性；每种化合物在给予多巴胺前体前60分钟给药。所研究的化合物类别包括非竞争性NMDA拮抗剂美金刚、金刚烷胺和MK-801，竞争性NMDA拮抗剂CGP 40116，抗惊厥和假定的抗惊厥剂拉莫三嗪和FCE 26743，它们具有部分谷氨酸能拮抗作用。所有六种化合物与左旋多巴共同给药时，均以剂量特异性或剂量依赖性方式提高了对左旋多巴耐受小鼠的运动、竖毛和总活动计数，但只有美金刚和MK-801影响了也接受慢性左旋多巴治疗的对照小鼠的运动活性。因此，在一系列实验中评估了这些化合物对经MPTP处理且对左旋多巴耐受的超阈值小鼠中左旋多巴疗效“减退”的恢复作用。在每一类潜在治疗剂中，对活动减少的MPTP小鼠的运动活性刺激作用获得了不同的恢复效果，证实了具有谷氨酸拮抗作用的化合物假定的抗帕金森病应用。
