INTRAVENOUS DOPAMINE AGONIST THERAPY--PARKINSONS DISEASE

描述(申请人摘要)：这是一份修改后的申请书 美国国立卫生研究院将支持安慰剂的第二阶段临床试验 静脉注射多巴胺激动剂治疗晚期脑梗塞 帕金森氏病(PD)。 特发性帕金森病(PD)是第二大最常见的疾病 成人中的神经退行性疾病，困扰约50万人 美国人。帕金森病的症状包括震颤、肌肉僵硬和动作迟缓 当大约75%的中脑多巴胺(DA) 黑质中的神经元死亡。由此导致的脑多巴胺缺乏 口服L多巴可成功治疗状态数年， 酪氨酸及其前体的天然氨基酸衍生物 多巴胺，和/或直接多巴胺激动剂(培高利特、溴隐亭)。之后 经过几年的口服治疗，初步顺利控制了帕金森病 症状让位于药物剂量的波动和 令人痛苦的副作用，如运动障碍和开关现象。这些 反应的波动和药物的副作用不充分 由口服治疗和可用药物控制，结果是永久性的 约10%-20%的PD患者的残疾和生活质量较差 人口。这种波动可以通过连续的 注射用L多巴/激动剂与中枢神经系统 药效学反应可以改变，以利于改善控制 帕金森氏症的症状。

DESCRIPTION (Applicant's abstract): This is a revised application to the national Institutes of Health to support Phase 2 clinical trials of intravenous dopamine agonist therapy for patients with advanced Parkinson's disease (PD). Idiopathic Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among adults and afflicts about 500,000 Americans. PD symptoms of tremor, muscular rigidity and slowness of voluntary movement arise when about 75 percent of midbrain dopamine (DA) neurons in the substantia nigra die. The resulting brain DA deficiency state can be treated successfully for several years with oral L-DOPA, the naturally occurring amino acid derivative of tyrosine and precursor of DA, and/or direct DA agonists (pergolide, bromocriptine). After several years of oral treatment, the initial smooth control of PD symptoms gives way to fluctuations in response to medication doses and distressing side effects such as dyskinesias and on-off phenomena. These fluctuations in response and drug side effects are not adequately controlled by oral therapy with available agents and result in permanent disability and poor quality of life for about 10-20 percent of the PD population. Such fluctuations can be variably controlled by continuous parenteral L-DOPA/agonist administration, and central nervous pharmacodynamic responses can be altered in favor of improved control of PD symptoms.