课件：神经系统药理—魏尔清抗帕金森病药.ppt

* Part 10Drugs Treating Parkinson Disease and Alzheimer Disease Levodopa and related drugs Cholinoceptor antagonists Drugs treating dementia Drugs for treatment of Parkinson disease (PD) Levodopa and related drugs Cholinoceptor antagonists Parkinson disease and therapeutic drugs Rigidity: one of the common symptoms of PD Tremor: one of the common symptoms of PD Pyramidal and extrapyramidal pathways Striatum 黑质-纹状体通路 中脑-皮层通路 结节-漏斗通路 Substantia nigro -striatum dopaminergic pathway is involved in PD pathogenesis Parkinson disease Dopaminergic neuron degeneration in substantia nigro and striatum Normal PD Control Produce dopamine Dopamine Acetylcholine Abnormal balance of DA/ACh neuronal functions in extrapyramidal system of Parkinson disease Levodopa Muscarinic antagonists Normal Parkinson disease (-) (-) injured relatively potentiated PD: GABA ? HD: GABA ? (+) (-) (-) (+) (-) ? (-) ? (-) ? Levodopa and related drugs Levodopa, L-dopa 左旋多巴 Drugs for treatment of Parkinson disease Levodopa Dopamine Levodopa 1. ADME Penetrating into the brain, transformed to DA or NE (less) Distributed in peripheral tissue (most) 2. Effects and uses Parkinson disease: decreases the rigidity, tremors, and other symptoms 3. Adverse effects (1) CNS: abnormal involuntary; hallucinations; etc. (2) GI: nausea, vomiting, etc. (3) CVS: hypotension, arrhythmia, etc. Drugs for treatment of Parkinson disease Inhibitors of aromatic L-amino acid decarboxylase Carbidopa 卡比多巴 can not cross BBB, but can inhibit peripheral dopamine synthesis. increases availability of levodopa to the CNS and decreases peripheral effects Drugs for treatment of Parkinson disease Levodopa alone Levodopa + Carbidopa Other drugs 1. DA receptor agonists Bromocriptine 溴隐亭 Pergolide 培高利特 Pramiperole 普拉克索 Ropinirole 罗平尼咯 Drugs for treatment of Parkinson disease 2. MAO inhibitors decreasing DA metabolism in the CNS Selegiline 司来吉兰 Rasagiline 雷沙吉兰 3. COMT inhibitors decreasing DA metabolism in the CNS Nitecapon