INTRAVENOUS DOPAMINE AGONIST THERAPY--PARKINSONS DISEASE

描述（申请人摘要）：这是对本申请的修订申请。 美国国立卫生研究院支持2期临床试验 多巴胺受体激动剂治疗晚期脑梗死 帕金森病（PD）。 特发性帕金森病（PD）是第二个最流行的 在成人中患有神经退行性疾病， 美国人 PD症状包括震颤、肌肉强直和 当中脑中大约75%的多巴胺（DA） 黑质的神经元死亡。 导致大脑DA缺乏 口服左旋多巴可成功治疗数年， 天然存在的酪氨酸的氨基酸衍生物和前体 和/或直接DA激动剂（培高利特、溴隐亭）。 后 几年的口服治疗，初步顺利控制PD 症状让位于药物剂量的波动， 令人痛苦的副作用，如运动障碍和开关现象。 这些 反应的波动和药物副作用不足以 通过可用药物的口服治疗控制，并导致永久性 残疾和生活质量差，约10- 20%的PD 人口 这种波动可以通过连续的 胃肠外L-DOPA/激动剂给药和中枢神经系统 可以改变药效学反应以有利于改善控制 PD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.