Drugs for CNS degenerative disorders治疗中枢神经系统退行性疾病药物.pptVIP

Drugs Used for Neurodegenerative Diseases of CNS治疗中枢神经系统退行性疾病药物 Neurodegenerative Diseases Associated with progressive loss of neurons and their functions Parkinson’s disease(帕金森病) Alzheimer’s disease(阿尔茨海默病) Huntington’s disease(亨廷顿病，舞蹈病) Amyotrophic lateral sclerosis (肌萎缩侧索硬化症) Common Mechanisms of Neurodegeneration Misfolded and aggregated proteins ?-synuclein in PD; ?-amyloid and tau in AD; huntingtin in HD; SOD and TDP-43 in ALS Excess glutamate in the brain Impairment in the capacity of neurons for oxidative metabolism Parkinsonism (Parkinson’s syndrome) not resulted from neurodegenerative disease used to describe the syndrome Parkinsons disease the second most prevalent neurodegenerative disease (after Alzheimers disease) the most common cause of parkinsonism Parkinson’s disease Symptoms: Resting tremor Muscle rigidity ---- increased tone, akinesia运动不能 Bradykinesia运动徐缓-----difficulty in initiating movements and controlling fine movements Postural instability Parkinson’s disease Background: 1. Neuronal circuits involved in movements: cortical regions, thalamus丘脑 , cerebellum小脑 , and basal ganglia基底节 (substantia nigra黑质, striatum纹状体, globus pallidus苍白球 and subthalamus下丘脑 ). striatum: caudate nucleus 尾核and putamen壳核 2. The basal ganglia play an important part in the initiation and scaling of movement. Parkinson’s disease Background: 3. Dopamine neurons in the substantia nigra project to the striatum纹状体(caudate nucleus and putamen) and exert an inhibitory influence on motoneurons. 4. Cholinergic interneurons in the striatum纹状体promote motoneuronal excitation Parkinson’s disease Pathophysiologic basis: Degeneration of dopaminergic neurons in the substantia nigra Nigrostriatal pathway黑质纹状体通路 Drugs for Parkinson’s disease Groups of Drugs Quasi-Dopamine drugs(拟多巴胺类药) ----levodopa（左旋多巴）, carbidopa（卡比多巴）, selegiline（司来吉兰） Central anticholinergic drugs (中枢抗胆碱药) ----benzhexol(苯海索), benzatropine(苯扎托品) Others ----amantadine(金刚烷胺), ropi