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Aminopyridines for symptomatic treatment in multiple sclerosis

  • Review
  • Intervention




The potassium channel blockers 4-aminopyridine (AP) and 3,4-diaminopyridine (DAP) increase nerve conduction in demyelinated nerve fibers, and have been proposed as a symptomatic therapy for people with multiple sclerosis (MS).


To determine the efficacy and safety of aminopyridines for neurological deficits in adults with MS.

Search methods

We searched the Cochrane MS Group trials register (December 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (January 1966 to December 2004) and EMBASE (1974 to December 2004). We hand searched bibliographic references from retrieved studies and recent MS symposia reports, and contacted known studies' investigators.

Selection criteria

We included trials fulfilling all following criteria: randomised controlled trials (RCTs); adults with MS, out of exacerbation; AP or DAP treatment versus placebo; clinical endpoints.

Data collection and analysis

Three reviewers independently extracted data and assessed trial quality from 17 full-paper studies.

Main results

Six studies (eight publications, 198 participants, all crossover trials) were considered. Five studies assessed the efficacy of AP versus placebo, one compared DAP with active placebo. Treatment duration ranged from hours to six months. Median quality score of the studies was three.

Of the 198 treated participants, there were six major side effects: one acute encephalopathy, three episodes of confusion, and two seizures.
Three studies (54 participants) assessed manual muscle testing, with 29 participants (54%) improving in at least one muscular district during study treatment versus four participants (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI] 4.7 to 43.7). Nine out of 54 participants (17%) improved in ambulation during study treatment versus none during placebo (p < 0.001). A lower Expanded Disability Status Scale (EDSS) score was found in 13/198 participants during study treatment (7%) versus none during placebo (p < 0.001). No improvement in neuropsychological tests was found in three trials assessing cognitive function. Finally, 47/136 adults with MS (35%) felt better when receiving the study drug, against 7(5%) on placebo (OR 9.7, 95% CI 4.3 to 22.0).

Authors' conclusions

Currently available information allows no unbiased statement about safety or efficacy of aminopyridines for treating MS symptoms. Furthermore, we could not obtain any data on three unpublished RCTs (more than 300 participants). We conclude that publication bias remains a pervasive problem in this area, and that until the results of these unpublished studies are available to the scientific community, no confident estimate of effectiveness of aminopyridines in the management of MS symptoms is possible.








我們搜尋了Cochrane MS Group trials register﹝2004年12月﹞,the Cochrane Central Register of Controlled Trials﹝CENTRAL﹞﹝The Cochrane Library 2004年,第四期﹞,MEDLINE﹝1966年1月到2004年12月﹞以及EMBASE﹝1974年到2004年12月﹞。我們還搜尋了所有收錄研究中的參考資料,以及最近的MS研討會的紀錄,也連絡論文的研究者。






6個研究被我們納入考量﹝8項發表、198位參與者、全部都是交叉試驗﹞。其中五個研究以AP和安慰劑做比較並評估療效,一個是以仿DAP副作用的安慰劑和DAP做比較。治療時間從幾小時到6個月都有。這些研究品質分數的中間數是3。在這198位參與者中,有6位出現主要副作用:1位有急性腦病變、3位認知混亂,以及2位有顛斜的情況。3個研究﹝54位參與者﹞有做徒手肌肉測試,使用治療藥物的組別中有29位﹝54%﹞有至少一個肌區獲得改善,而使用安慰劑的則有4位﹝7%﹞﹝odds ratio [OR] 14.5,95% CI 4.7到43.7﹞。使用治療藥物的54人中有9位在行走能力上有獲得改善,而安慰劑組在這方面則沒有人有改善﹝p < 0.001﹞。在神經心理測驗方面,3個試驗在認知功能上都沒有發現改善。最後,47/136罹患MS的成人﹝35%﹞覺得在服用試驗藥物後有得到改善,而安慰劑的組別則有7人﹝9%﹞覺得有所改善﹝OR 9.7, 95% CI 4.3到22.0﹞。





此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


我們仍然不清楚鉀離子阻斷劑﹝AP和DAP﹞用於治療各種多發性硬化症症狀的安全性和實用性。多發性硬化症﹝MS﹞是一個會影響年輕和中年人的疾病,依個體情況有不同症狀。這是由髓鞘﹝包付在神經外,能保護神經和脊髓的纖維構造﹞的破壞而引起的。鉀﹝一種礦物質﹞在神經的運作上扮演重要的角色,但缺乏髓鞘時會變得太過活躍。鉀離子阻斷劑﹝4aminopyridine AP和3,4daminopyridine DAP﹞可能可以改善缺乏髓鞘的神經的運作。然而,我們所找到的試驗都沒有足以證明這些藥物的安全性或能確定其好處的證據。

Plain language summary

The effect of aminopyridine for the treatment of several symptoms in people with multiple sclerosis

Multiple sclerosis (MS) is a disease that affects young and middle-aged adults, causing different symptoms in individuals. It is caused by damage to the myelin sheaths (fibres that wrap around and protect the nerves and spinal cord). Potassium (a mineral) is important for nerve function, but may become too active when there is not enough myelin. Potassium blocking drugs (4-aminopyridine AP, and 3,4-daminopyridine DAP) may be able to improve nerve function in nerves without enough myelin. However, the review of trials found there is not enough evidence about the safety of these drugs or whether benefits are certain.