文档介绍：潘燕
北京大学基础医学院药理学系
抗帕金森病药 Antiparkisonism Drugs
Muhammad Ali and Michael J. Fox suffered from Parkinson’s disease, before the start of a Senate hearing on the disorder in 2002
帕金森病(原发性)(parkinsonism) 帕金森氏综合征(继发性)(Parkinson’s syndrome)
“neurodegenerative diseases”神经退行性疾病
Paralysis agitans震颤麻痹
神经退行性疾病one of the “neurodegenerative diseases”
1817,James Parkinson(Britain) First described Paralysis agitans in his“an essay on the shaking Palsy”
SHAKING PALSY. (Paralysis Agitans.)
Parkinson’s disease(帕金森病,PD)
Monograph by James Parkinson
1817
Diagnostic Features
症状:
resting tremor 静止性震颤、rigidity 肌强直、bradykinesia 运动迟缓、abnormal postural reflexes 异常体位反射(姿势步态不稳)
面具脸
节律性震颤,搓丸样运动
铅管样强直
慌张步态
易激怒发音障碍
发声过弱
劳动性呼吸困难
Pathogenesis
锥体外系的黑质-纹状体DA能神经元变性、缺失,DA合成↓,纹状体内DA↓,DA能神经功能↓;
依据:
⑴阻断DA-R的抗精神病药、利血平
⑵MPTP→选择性破坏黑质-纹状体DA能神经元
⑶大鼠旋转模型
⑷帕金森病患者中脑纹状体DA↓
⑸病理学改变:大体/组织学
PD
Research Development of PD
Nobel Prize in Physiology
or Medicine (2000)
Arvid Carlsson:
developed a method for measuring amount of dopamine
dopamine in the basal ganglia, were particularly high.
reserpine caused a decrease in dopamine levels and a loss of movement control
L-Dopa could alleviate the symptoms.
甲苯哌啶丙酸酯
甲苯四氢吡叮
黑质-纹状体
MPTP(1-甲基-4苯基-1,2,3,6四氢吡啶)
MPP+(1-甲基-4苯基吡啶)
选择性破坏
DA神经元
帕金森病/帕金森综合征动物模型
脑内单胺氧化酶-B(MAO-B)
帕金森病/帕金森综合征动物模型
Left right
纹状体
黑质
6-羟多巴胺单侧损毁黑质DA能神经元
应用阿朴吗啡(apomorphine, DA-R兴奋剂)→向健侧旋转
应用苯丙胺(amphetamine,促进DA释放) →向病侧旋转