Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis

Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine‐ER, an extended‐release formulation of dalfampridine (also known by its chemical name, 4‐aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a na...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2014-11, Vol.1329 (1), p.33-44
Main Authors: Blight, Andrew R., Henney III, Herbert R., Cohen, Ron
Format: Article
Language:English
Subjects:
4-aminopyridine
4-Aminopyridine - therapeutic use
Clinical Trials as Topic - trends
dalfampridine
Drug Discovery - trends
fampridine
Humans
Medical research
Multiple sclerosis
Multiple Sclerosis - diagnosis
Multiple Sclerosis - drug therapy
Multiple Sclerosis - physiopathology
Potassium Channel Blockers - therapeutic use
Treatment Outcome
walking
Walking - physiology
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Summary:Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine‐ER, an extended‐release formulation of dalfampridine (also known by its chemical name, 4‐aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a narrow therapeutic window, and assessed for its ability to improve walking in MS. The putative mechanism of action of dalfampridine‐ER is restoration of axonal conduction via blockade of the potassium channels that become exposed during axonal demyelination. Two pivotal phase III clinical trials demonstrated that dalfampridine‐ER 10‐mg tablets administered twice daily improved walking speed and patient‐reported perceptions of walking in some patients. Dalfampridine‐ER was generally well tolerated, and, at the approved dose, risk of seizure was neither elevated relative to placebo nor higher than the rate in the MS population. Dalfampridine‐ER (AMPYRA®) was approved in the United States for the treatment of walking in patients with MS as demonstrated by an increase in walking speed. The use of the dalfampridine‐ER is contraindicated in patients with a history of seizure. It is the first pharmacologic therapy for this indication and has been incorporated into clinical management of MS.
ISSN:0077-8923
1749-6632
DOI:10.1111/nyas.12512