Quinidine sulfate therapy for the slow-channel congenital myasthenic syndrome
Quinidine sulfate therapy for the slow-channel congenital myasthenic syndrome
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DOI：
10.1002/ana.410430411
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发表时间：
1998-04-01
影响因子：
11.2
通讯作者：
Engel, AG
中科院分区：
文献类型：
--
作者：
Harper, CM;Engel, AG
慢通道先天性肌无力综合征（SCCMS）是由终板乙酰胆碱受体（AChR）亚单位的功能获得突变引起的，这些突变延长了AChR通道的开放事件，导致去极化阻滞和终板肌病。因为临床实践中可达到的硫酸奎尼丁水平缩短了体外基因工程突变SCCMS受体的开放事件，我们测试了药物对SCCMS有益的概念。我们在一项开放标签试验中用硫酸奎尼丁治疗了6例SCCMS患者，使用肌肉力量的客观临床测量和重复刺激研究作为终点。1例患者在7天后对奎尼丁过敏。其余患者对药物耐受良好，连续治疗30天后，肌肉力量和快速刺激引起的复合肌肉动作电位的减少显示出统计学显著性改善。
The slow-channel congenital myasthenic syndrome (SCCMS) is caused by gain of function mutations in subunits of the end-plate acetylcholine receptor (AChR), The mutations prolong the opening episodes of the AChR channel, leading to a depolarization block and an end-plate myopathy Because levels of quinidine sulfate attainable in clinical practice shorten the opening episodes of genetically engineered mutant SCCMS receptors in vitro, we tested the notion that the drug can be of benefit in SCCMS. We treated 6 SCCMS patients with quinidine sulfate in an open-label trial, using objective clinical measures of muscle strength and repetitive stimulation studies as end points. One patient became allergic to quinidine after 7 days. The remaining patients tolerated the drug well and after 30 days of continuous therapy showed statistically significant improvement in muscle strength and in decrement of the compound muscle action potential elicited by rapid rates of stimulation.