Montplaisir J, Denesle R, Petit D
Centre d'étude du sommeil, Hôpital du Sacré-Coeur de Montréal, Department of psychiatry, Université de Montréal, Montréal, Québec, Canada.
Eur J Neurol. 2000 May;7 Suppl 1:27-31. doi: 10.1046/j.1468-1331.2000.0070s1027.x.
The restless legs syndrome (RLS) is a condition characterized by unpleasant limb sensations occurring at rest and associated with an irresistible urge to move. Several treatments are used to treat RLS including benzodiazepines, opioids, dopaminergic agents, clonidine and anticonvulsant drugs such as carbamazepine and gabapentine. Dopaminergic agents are now considered the treatment of choice for RLS. Levodopa is effective in treating RLS; however, several patients treated with levodopa at bedtime developed morning or late afternoon restlessness. Recently, more attention has been paid to dopamine receptor agonists. Ergoline derivatives, bromocriptine and pergolide were found effective, but require concomitant administration of domperidone, a peripheral dopamine antagonist. In a recent study, we studied the efficacy and innocuity of pramipexole, a new dopamine agonist with a higher affinity for the D3 receptor subtype of the D2 family, in a double-blind, placebo-controlled, randomized trial. Pramipexole had major effects on RLS symptoms without severe side-effects. The present study aimed to assess the long-term efficacy of pramipexole. Seven patients were treated with the drug for a mean follow-up duration of 7.8 months. Treatment was started at a dosage of 0.25 mg, and progressively increased until the optimal therapeutic effect was obtained. Home questionnaires were completed for 7 consecutive days, after one month and after a mean of 7.8 months of treatment with pramipexole, assessing leg restlessness during the daytime, in the evening, at bedtime and during the night. There was no evidence of a decrease in the therapeutic effect of pramipexole in these patients, even 7.8 months after the initiation of treatment. The optimal dosage was 0.25 mg for one patient, 0.5 mg for five patients and 0.75 mg for one patient. While there was a progressive increase in severity of leg restlessness from daytime to nighttime before treatment, a suppression of leg restlessness was observed throughout the 24 h with a single dose of pramipexole at bedtime. The remarkable efficacy of pramipexole raises the possibility that the D3 receptors of the mesolimbic system may be more specifically involved in the physiopathology of RLS.
不安腿综合征（RLS）是一种以休息时出现不愉快的肢体感觉并伴有无法抗拒的活动冲动为特征的病症。有多种治疗方法用于治疗RLS，包括苯二氮䓬类、阿片类、多巴胺能药物、可乐定以及抗惊厥药物如卡马西平和加巴喷丁。多巴胺能药物现在被认为是RLS的首选治疗方法。左旋多巴对治疗RLS有效；然而，一些在睡前服用左旋多巴的患者会出现早晨或傍晚的不安。最近，多巴胺受体激动剂受到了更多关注。麦角林衍生物、溴隐亭和培高利特被发现有效，但需要同时服用外周多巴胺拮抗剂多潘立酮。在最近的一项研究中，我们在一项双盲、安慰剂对照、随机试验中研究了普拉克索（一种对D2家族的D3受体亚型具有更高亲和力的新型多巴胺激动剂）的疗效和安全性。普拉克索对RLS症状有显著作用且无严重副作用。本研究旨在评估普拉克索的长期疗效。7名患者接受该药物治疗，平均随访时间为7.8个月。治疗从0.25毫克的剂量开始，逐渐增加剂量直至获得最佳治疗效果。在用普拉克索治疗1个月后以及平均治疗7.8个月后，连续七天填写家庭问卷，评估白天、傍晚、睡前和夜间的腿部不安情况。在这些患者中，即使在治疗开始7.8个月后，也没有证据表明普拉克索的治疗效果有所下降。最佳剂量对于一名患者为0.25毫克，五名患者为0.5毫克，一名患者为0.75毫克。在治疗前从白天到夜间腿部不安的严重程度逐渐增加，而在睡前单次服用普拉克索后，在24小时内均观察到腿部不安得到抑制。普拉克索的显著疗效增加了中脑边缘系统的D3受体可能更具体地参与RLS病理生理学的可能性。
