回复201楼 田亮
回复201楼 田亮:服用唑尼沙胺的体验
讲唑尼沙胺之前先看看《自然》杂志分刊（药物发现评论）对一些新药的意见。
可以留意Pardoprunox这只药物，可能也是很有前途对帕症的。
Safinamide(沙芬酰胺）前面已经讲过了，正常的话明年下半年会在欧洲首先上市。
而IPX066这只新药会在明年1月底由FDA审批，是美多巴和息宁的替代药物，商品名是Rytary,临床试验得到的结果还是值得肯定的，对左旋多巴补充疗法（中晚期帕症）多一个选择。
以上是题外话。
唑尼沙胺主要肯定在改善运动状况和减少关期，针对异动症以及冲动控制障碍（ICD)还有很大潜力。
就我对唑尼沙胺的理解，其在控制和改善病情之余，对病情的恢复是有利的，而且从药物的本身特性来讲，有一些试验已经证实其对多巴胺神经元的恢复过程有利(这一点非常重要),也是目前很多对症药物并不具备的特性，只要在没有较大的副作用下，可以应用一段时间，将来的结果可以说是谨慎乐观的。
TABLE 2 | Phase II and Phase III trials of novel emerging agents and targets
From the following article:
Priorities in Parkinson’s disease research
Wassilios G. Meissner, Mark Frasier, Thomas Gasser, Christopher G. Goetz, Andres Lozano, Paola Piccini, José A. Obeso, Olivier Rascol, Anthony Schapira, Valerie Voon, David M. Weiner, François Tison & Erwan Bezard
Nature Reviews Drug Discovery 10, 377-393 (May 2011)
doi:10.1038/nrd3430
Compound Mechanism of action Phase Trial results Refs
Serotonergic agonists and antagonists
Sarizotan 5-HT1A receptor agonist, partial D2 agonist III Failed to demonstrate efficacy against dyskinesia 14
Piclozotan 5-HT1A receptor agonist III Increases ON time and reduces OFF time without affecting dyskinesia 130
Pardoprunox 5-HT1A receptor agonist, partial D2 and D3 agonist II Improves motor scores in early PD, effects on motor fluctuations and dyskinesia unknown. Current stage of development uncertain (results of two completed Phase III trials in early (NCT00269516) and advanced-stage PD (NCT00406588) not yet reported) 131
Pimavanserin (ACP-103) 5-HT2A receptor inverse agonist II Trend towards improvement of psychosis without impairing mobility 132
III Initial late-stage trial failed to meet primary end point 69
II Assessment of antidyskinetic effects (NCT00086294; no results yet reported) -
Glutamate antagonists and release inhibitors
FP0011 Glutamate release inhibitor IIa Increases ON time without producing troublesome dyskinesia 133
Safinamide Sodium channel inhibitor, MAOB inhibitor, glutamate release inhibitor II Improves motor scores in early PD 70
III Increases ON time without producing troublesome dyskinesia in advanced-stage PD 70
Memantine NMDA receptor antagonist IV Failed to show a statistically significant benefit on cognition in PDD 30
Taxoprodil NMDA receptor 2B antagonist II Antidyskinetic properties; frequent side effects including abnormal thinking, de-personalization and amnesia, which precluded further development 134
Perampanel AMPA receptor antagonist II No effect on the wearing-off phenomenon, dyskinesia or cognition 135
AFQ056 mGluR5 (negative allosteric modulator) Ib/II Antidyskinetic effects; UPDRS motor scores improved by more than three points versus placebo, but the study was not sufficiently powered to reach statistical significance 136
Acamprosate GABA and taurine analogue, reduces glutamate-mediated neurotransmission IV Evaluation for compulsive behaviour and craving in PD (NCT00640952; study withdrawn) -
Adenosine receptor agonists and antagonists
Istradefylline A2A antagonist II, III Decreases OFF time without increasing ON time with troublesome dyskinesia; the largest trial involving 610 patients with PD was negative 137–140, 141
Vipadenant (BIIB014) A2A antagonist II Results of Phase II trial not yet reported (NCT00442780, NCT00438607), development was recently stopped -
Preladenant (SCH-420814) A2A antagonist II Decreases OFF time; results for dyskinesia not yet reported (NCT00845000) 142
Other agents
Fipamezole α2A-AR antagonist II No differences between drug and placebo probably owing to heterogeneity between participants in the United States and India, and/or investigators at the different enrolling sites 143
IPX066 Levodopa/carbidopa extended release III Reduces OFF time -
Topiramate Antiepileptic II Evaluation of effect on dyskinesia (no results yet reported) -
Zonisamide Antiepileptic, inhibition of MAOB and glutamate release III Improves motor scores and reduces OFF time; approved for the treatment of PD in Japan since 2009 144
Disease modification and neuroprotection
Creatine Modulator of mitochondrial function II Selected after successful screening in a small clinical trial using futility analysis 145,146
