PHARMACOLOGY, BIOCHEMISTRY AND PHYSIOLOGY OF CENTRAL NEUROTRANSMITTERS

1.从出现症状到出现的间隔时间 左旋多巴与左旋多巴启动至运动的时间无关 并发症发作。似乎不再有理性的基础 帕金森病患者延迟左旋多巴治疗。 2.运动反应并发症反映了纹状体系统的改变 多巴胺能去传入与间歇性拟多巴胺治疗 并随着更多的生理刺激而趋于正常化 持续的更替战略。 3.谷氨酸能机制影响锥体外系运动功能 大鼠，D-2介导的反应需要并发的NMDA受体 刺激，而D-1受体调节的通路有不同程度的 对NMDA受体阻滞剂的敏感性；丘脑底核 主要参与D-2介导的运动行为的表达。 在帕金森病患者中，谷氨酸能刺激 Milacemide短暂地增加了帕金森病的整体严重程度， 尤其是僵化。 4.线粒体呼吸功能不存在全身性缺陷 记录在帕金森氏病中：耗氧率和 血小板和肌肉线粒体呼吸链酶活性的研究 以及葡萄糖负荷后的血乳酸水平没有变化 患者和对照组之间的差异显著。 5.Tourette综合征患者腹侧脑功能明显下降 区域，沿皮质上凸起增加，并倒置 这些边缘和感觉运动区之间的关系 出现在PET-氟脱氧葡萄糖扫描上。 6.毒扁豆碱以最大耐受量持续静脉滴注 水平仅抑制脑脊液乙酰胆碱酯酶21%，且几乎不产生 认知方面的好处。健忘剂量的抗胆碱能药物东莨菪碱， 增加正常老年受试者的皮质功能与 阿尔茨海默病的正电子发射计算机断层扫描中的下降，尤其是顶颞部 病人。毒扁豆碱非但没有正常化，反而略微减少了 皮质新陈代谢。

1. The interval from the onset of symptoms to the introduction of levodopa was unrelated to the time from levodopa initiation to motor complication onset. There no longer appears to be a rational basis for delaying levodopa therapy in parkinsonian patients. 2. Motor response complications reflect striatal system changes due to dopaminergic deafferentation and intermittent dopaminomimetic treatment and tend to normalize with the more physiologic stimulation afforded by continuous replacement strategies. 3. Glutamatergic mechanisms affect extrapyramidal motor function: In rats, D-2 mediated responses require concurrent NMDA receptor stimulation, while D-1 receptor-regulated pathways have varying degrees of sensitivity to NMDA receptor blockade; the subthalamic nucleus contributes primarily to the expression of D-2 mediated motor behaviors. In patients with Parkinson's disease, glutamatergic stimulation with milacemide transiently increased overall parkinsonian severity, especially rigidity. 4. No generalized defect in mitochondrial respiratory function could be documented in Parkinson's disease: oxygen consumption rates and respiratory chain enzyme activities in platelets and muscle mitochondria as well as blood lactate levels following glucose loading did not differ significantly between patients and controls. 5. Tourette syndrome patients have marked decreases in ventral brain areas, increases along the superior cortical convexities, and inverted relationships between these limbic and sensorimotor cortical regions appear on PET-fluorodeoxyglucose scans. 6. Physostigmine by continuous intravenous infusion at maximum tolerated levels inhibits CSF acetylcholinesterase by only 21% and produces little cognitive benefit. Amnestic doses of the anticholinergic, scopolamine, increase cortical function in normal elderly subjects in contrast to the decreases, especially parietotemporal, in PET scans of Alzheimer patients. Physostigmine, rather than normalizing, marginally diminishes cortical metabolism.