Agents for Parkinson’s Disease
治疗中枢神经系统退行性疾病药物 17
Parkinson’s Disease（PD） :
Originally described in 1817 by British physician,
James Parkinson, who called it “the shaking
palsy."About 1960 the disease was traced to the
loss of dopamine-producing neurons in the
substantia nigra
Symptoms of PD:
Trembling of hands, arms, legs, jaw and face
Stiffness of the arms, legs and trunk
Slowness of movement
Poor balance and coordination
第1节 抗帕金森氏病药
Anti-PD Drugs
1. Mechanism of PD
Dopamine：Inhibition
ACh: Excitation
1. +DA
2. Anti-Ach
3. Stimulate D-R
Slow
Fast
L-aminoacid transporter on BBB?
D1-3, which is important for PD?
二、拟多巴胺类药物
LEVODOPA
Aromatic L-amino acid decarboxylase
（AADC)
Active
Into Blood
DopmineBBB
Active
CNS
Dopamine
( inside or outside of C?)
Carbidopa
Benserazide
帕金宁, 心宁美
Indications of L-Dopa
All types of PD, except for those induced by
Chlorpromazine
Antagonist of D2
D2 is responsible for PD
Side Effects of Levodopa
1. Gastrointestinal Effects
Direct stimulation
Stimualtion of the chemoreceptor trigger
zone located in the brainstem by DA
Domperidone (吗叮啉）- Antagonist of D2
To increase the dose slowly
2. Cardiovascular Effects
Increased catecholamine formation-cardiac arrhythmia
Beta antagonist
Long Periods
1. Dyskinesia:
2. A movement disorder which consists of effects
including diminished voluntary movements and the
presence of involuntary movements, similar to tics or
chorea .为什么初期治疗没有？
2. On-off response
3. Adverse mental effects
Drug Interactions
Vitamin B6:
A water-soluble vitamin and is part of the vitamin B
complex group. Pyridoxal phosphate (PLP) is the active
form and is a cofactor in many reactions of amino acid
metabolism, including transamination, deamination, and
decarboxylation. PLP also is necessary for the enzymatic
reaction governing the release of glucose from glycogen.
Selegiline: Inhibitor of MAO-B in CNS
Nitecapone: Inhibitor of COMT outside of CNS
Tocapone: Inhibitor of COMT of whole body
Bromocriptine
Lisuride
Pergolide
3. Agonist of DR
DR - D1-5
D2
Agonist of D2
AD?
4. Agents to increase the release of DA
三、抗胆碱药
Cholinoceptor antagonists
Benzhexol
Benzatropine
Atropine Scopolamine?
1.甲磺酸培高利特：美韩发现心血管不良反应，
中国如何撤药？
2.美多巴，心宁美的组方原理？
3.为什么美多巴之类用到最后，还是无效？
4.开关现象？如何调整给药方案？
是否可用于精神疾病患者？
闭角型青光眼患者？
消化性溃疡患者?
