Abstract

Background

Restless legs syndrome (RLS) is a common condition that initially responds dramatically to dopaminergic therapy. Over time, however, dopaminergics cause augmentation, where symptoms occur earlier and intensify. Animal models suggest this may result from increased dopamine receptor type-1 affinity in the spinal cord. Ecopipam is a potent, specific dopamine-1/5 receptor antagonist.

Methods

We performed a small (N = 10) exploratory placebo controlled, cross-over safety trial of ecopipam (25–100 mg/day) for patients with augmented RLS currently taking dopamine agonists.

Results

Ecopipam was well tolerated with sedation being the most common adverse event in drug and placebo. Safety scales and serology data were similar to placebo. The study was not powered to demonstrate efficacy and exploratory efficacy data showed no significant improvement compared to placebo, but RLS diaries, the international RLS rating scale, and clinical global impressions all favored drug. No subject worsened on drug or demonstrated rebound worsening after drug discontinuation.

Conclusion

Ecopipam was safe and well tolerated in this initial study for RLS. Given the lack of alternate options, larger efficacy studies for augmented RLS, and potentially de novo RLS are justified.

中文翻译：

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探索性交叉，使用多巴胺受体 1/5 拮抗剂 ecopipam D1/D5 拮抗剂 ecopipam 对增强 RLS 进行增强 RLS 试验

摘要

背景

不宁腿综合征 (RLS) 是一种常见疾病，最初对多巴胺能治疗有显着反应。然而，随着时间的推移，多巴胺能药物会导致症状加重，症状会更早出现并加剧。动物模型表明这可能是由于脊髓中多巴胺受体 1 型亲和力增加所致。Ecopipam 是一种有效的特异性多巴胺 1/5 受体拮抗剂。

方法

我们对目前正在服用多巴胺激动剂的 RLS 增强患者进行了一项小型 ( N  = 10) 探索性安慰剂对照、交叉安全性试验，该试验使用了 ecopipam（25-100 毫克/天）。

结果

Ecopipam 耐受性良好，镇静是药物和安慰剂中最常见的不良事件。安全量表和血清学数据与安慰剂相似。该研究无法证明疗效，探索性疗效数据显示与安慰剂相比没有显着改善，但 RLS 日记、国际 RLS 评级量表和临床全球印象都支持药物。没有受试者因药物而恶化或在停药后表现出反跳恶化。

结论

在这项针对 RLS 的初步研究中，Ecopipam 是安全且耐受性良好的。鉴于缺乏替代选择，对增强 RLS 和潜在的从头 RLS 进行更大规模的疗效研究是合理的。