Metman L V, Blanchet P J, de Jong D, Mouradian M M, Chase T N
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mov Disord. 1996 May;11(3):257-60. doi: 10.1002/mds.870110307.
The ergoline derivative FCE 23,884 acts as a dopamine D1 agonist in untreated parkinsonian animals and as a D2 antagonist in animals whose dopamine system is intact or levodopa treated. To evaluate whether this dual action might benefit patients with Parkinson's disease (PD) who have developed levodopa-induced dyskinesias, the motor effects of FCE 23,884 were examined in seven such individuals using a double-blind, placebo-controlled design. At doses up to the maximum tolerated dose (3.5 +/- 0.5 mg), FCE 23,884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23,884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 +/- 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23,884 in the symptomatic treatment of PD. Although D2 receptor blockade provided by FCE 23,884 antagonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology.
麦角灵衍生物FCE 23,884在未经治疗的帕金森病动物中作为多巴胺D1激动剂起作用，而在多巴胺系统完整或接受左旋多巴治疗的动物中作为D2拮抗剂起作用。为了评估这种双重作用是否可能使已出现左旋多巴诱导的运动障碍的帕金森病（PD）患者受益，采用双盲、安慰剂对照设计，对7名此类患者检查了FCE 23,884的运动效应。在高达最大耐受剂量（3.5±0.5毫克）的剂量下，FCE 23,884单药治疗不影响帕金森病严重程度。另一方面，在稳态条件下静脉输注FCE 23,884与轻度运动障碍剂量的左旋多巴合用，使抗帕金森反应降低了54±19%，并倾向于减轻运动障碍严重程度。因此，结果未能表明FCE 23,884在PD的对症治疗中有任何有用作用。虽然FCE 23,884提供的D2受体阻断作用可拮抗对左旋多巴的抗帕金森和致运动障碍反应，但D1受体刺激程度似乎不足以改善帕金森病症状。
