治疗帕金森病的药物.pptVIP

* (2) MAO-B inhibitors (＝BBB) L-DOPA DA AADC COMT 3-OMD L-DOPA 3-OMD DA AADC X degradation MAO-B COMT reuptake ( 3-O-甲基多巴) BBB Brain Periphery compete Carrier * Selegiline (司来吉兰) BBB permeable, inhibit MAO-B: CNS reduce L-dopa dose and “on-off phenomena” low dose (＜10mg/d) —only inhibit MAO-B→DA↑ high dose (＞10mg/d)—inhibit MAO-A, too→ hypertensive crisis antioxidant effect * X * (3) COMT inhibitors (≠or＝ BBB) L-DOPA DA AADC COMT 3-OMD L-DOPA 3-OMD DA AADC X degradation MAO-B COMT reuptake ( 3-O-甲基多巴) BBB Brain Periphery compete Carrier * Periphery: CNS: DA degradation↓→ DA in CNS↑ L-DOPA degradation↓ 3-OMD (3-O-甲基多巴)↓ carrier available for L-DOPA↑ L-DOPA that reach the brain↑ nitecapone (硝替卡朋): periphery Entacapone(恩他卡朋): periphery Tocapone(托卡朋): periphery and CNS * Dopamine receptors five main subtypes: D1 ~D5 D1-like receptors: D1, D5 D2-like receptors: D2, D3, D4 3. DA receptor agonists Nigro-striatal system: 激活D1-like receptor (D1,D5): 兴奋 激活D2-like receptor (D2, D3): 抑制 * Bromocriptine (溴隐亭): D2 agonism , D1 partial antagonism Pramipexole (普拉克索，森福罗 ): D2 agonism Ropinirole (罗平尼咯): D2 agonism Lisuride (利修来得): D2 agonism, D1 weak antagonism Less dyskinesia and on-off phenomenon Important in first line therapy * Bromocriptine (溴隐亭) 1. Small dose: stimulate D2-like R in tuberoinfundibular 　　　　　　　　　　　　　（结节漏斗部） ? prolactin (PRL) and GH release 2. Large dose: stimulate D2-like R in substantia nigro-striatal Uses: PD, hyperprolactinemia (高催乳素血症) acromegaly (肢端肥大症) * 4. Drugs enhancing DA release Amantadine (金刚烷胺) Mechanism: 1.↑release DA from dopaminergic terminals. 2.↓reuptake of DA. 3. dopamine receptor agonism Characteristics: 1. effect L-dopa but anticholinergic agents. 2. rapid onset, synergistic action with L-dopa * Ⅱ Central Anticholinerg