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首页> 外文期刊>Archives of Neurology >Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease.
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Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease.

机译：感应的多巴胺D1受体激动剂abt - 431运动障碍与左旋多巴的病人帕金森病。

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BACKGROUND: Dyskinesias are a frequent adverse effect of long-term levodopa therapy. The relative contribution of dopamine D(1) and D(2) receptor function to the pathophysiology of levodopa-induced dyskinesias remains a matter of controversy. OBJECTIVE: To establish whether a selective D(1) dopamine agonist induces more or less dyskinesia than levodopa in primed dyskinetic patients with Parkinson disease. METHODS: We studied ABT-431, the prodrug of a fully selective D(1) agonist, in 20 subjects with advanced Parkinson disease and a fluctuating response to levodopa complicated by dyskinesias. Eight patients were studied in a double-blind, randomized design (French centers); 12, in an open, randomized design (US centers). We assessed and compared the antiparkinsonian (Unified Parkinson's Disease Rating Scale) and dyskinetic (response induced by an acute challenge of a suprathreshold dose of levodopa and by 4 different ascending doses (5, 10, 20, and 40 mg) of ABT-431 during the 6 hours after the challenge. RESULTS: The separate analysis of the double-blind and open data led to the same findings, ie, the antiparkinsonian and dyskinetic responses induced by ABT-431 were dose related. At the most effective doses (20 and 40 mg), ABT-431 exhibited similar antiparkinsonian benefit and produced similar dyskinesias as levodopa. CONCLUSION: Dopamine D(1) agonists can induce a full antiparkinsonian response but do not support previous hypotheses suggesting that D(1) agonists are more or less likely to produce dyskinesias than levodopa.
机译：背景:动作障碍是常见的不良长期左旋多巴治疗的效果。多巴胺的相对贡献(1)和D (2)受体功能的病理生理学levodopa-induced动作障碍仍然是一个问题争议。选择D(1)多巴胺受体激动剂诱导或多或运动障碍比左旋多巴在影射帕金森病运动障碍的患者。方法:我们研究了abt - 431 a的前体药物完全选择性D(1)受体激动剂,在20个科目先进的帕金森病和波动左旋多巴反应复杂运动困难。八个病人在双盲研究,随机设计(法国中心);开放、随机设计(我们中心)。并比较了抗帕金森病的(统一帕金森病评定量表)和运动障碍的(响应引起的一种急性的挑战超阈值的剂量左旋多巴和4不同剂量的提升(5、10、20和40毫克)abt - 431在6小时后挑战。双盲和开放的数据导致相同的结果,即抗帕金森病的运动障碍的反应引起的abt - 431剂量相关。最有效剂量(20和40毫克),abt - 431表现出相似的抗帕金森病的效益和产生类似运动困难左旋多巴。产生一个完整的响应,但抗帕金森病的表明不支持以前的假设D(1)受体激动剂或多或少可能产生比左旋多巴运动困难。

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