Aminopyridines for symptomatic treatment in multiple sclerosis

Solari, Alessandra; Uitdehaag, Bernard M. J.; Giuliani, G.; Pucci, Eugenio; Taus, Cristiana

doi:10.1002/14651858.cd001330

Cited by 65 publications

(51 citation statements)

References 31 publications

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“…The reported incidence of seizures with therapeutic use ranges between 1 and 3 %, which is comparable to the baseline incidence of seizures in patients with MS [56][57][58]. In clinical trials of the extendedrelease formulation of 4-AP, seizures appear to be dose related [27,40,55].…”

Section: Discussionmentioning

confidence: 96%

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

et al. 2012

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Section: Discussionmentioning

confidence: 96%

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

et al. 2012

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“…Perhaps a distinct protein is the primary target for 4-AP in MS. However, caution is called for here because little is actually understood about how 4-AP works in vivo to better MS, and the targeted dose of 4-AP used in the clinic is limited by the side effects of this drug rather than its maximal efficacy in treating disease (1)(2)(3)43). The current findings add neuronal Deg/ENaC channels to the list of possible targets that should be considered when probing how 4-AP betters MS and other diseases and pathologies of the nervous system.…”

Section: Discussionmentioning

confidence: 99%

“…3 is a progressive autoimmune neuroinflammatory disease of the central nervous system characterized by demyelination of neurons (1)(2)(3)(4). Demyelination impedes conduction of actions potentials by axons disrupting the function of presynaptic neurons and ultimately, diminishing the activity of postsynaptic cells to include skeletal muscle.…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 99%

“…It has been proposed that 4-AP betters symptoms primarily by overcoming axonal block to increase action potential conduction in neurons that have undergone demyelination (1)(2)(3)(4). Alternatives, which are not necessarily mutually exclusive, are that 4-AP enhances neurotransmitter release from presynaptic neurons, improves end organ function by increasing skeletal muscle twitch, and enhances CNS motor-evoked brain activity and/or exerts immunomodulatory actions.…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 99%

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Inhibition of Neuronal Degenerin/Epithelial Na+ Channels by the Multiple Sclerosis Drug 4-Aminopyridine

Boiko¹,

Kucher²,

Eaton

et al. 2013

Journal of Biological Chemistry

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Background: 4-AP treats the symptoms of MS because it inhibits Kv channels. Deg/ENaC channels contribute to the progression of MS. Results: 4-AP also inhibits Deg/ENaC channels. Conclusion: Effects on both Kv and Deg/ENaC channels should be considered when evaluating the actions of 4-AP. Significance: 4-AP may influence the symptoms and progression of MS because of inhibitory actions on Kv and Deg/ENaC channels, respectively.

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“…In 2001 a Cochrane review on the topic was published [Solari et al 2001] which was updated in 2003 [Solari et al 2003]. Mainly studies on 4-AP were included and only one study on SR-AP was identified.…”

Section: Introductionmentioning

confidence: 99%

4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review

Jensen

Ravnborg

Dalgas

2013

Ther Adv Neurol Disord

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This systematic review summarizes the existing evidence on the effect of 4-aminopyridine (4-AP) as a symptomatic treatment of decreased walking capacity in patients with multiple sclerosis (MS) when administered as an immediate release compound and a slow release compound. It summarizes existing evidence on the basic mechanisms of 4-AP from experimental studies and evidence on the clinical use of the compound. A systematic literature search was conducted of the following databases: PubMed and EMBASE. Thirty-five studies were included in the review divided into 16 experimental studies, two clinical studies with paraclinical endpoints and 17 clinical studies with clinical endpoints. Animal studies show that 4-AP can improve impulse conduction through demyelinated lesions. In patients with MS this translates into improved walking speed and muscle strength of the lower extremities in a subset of patients at a level that is often of clinical relevance. Phase III trials demonstrate approximately 25% increase in walking speed in roughly 40% and improved muscle strength in the lower extremities. Furthermore, 4-AP might have an effect on other domains such as cognition, upper extremity function and bowel and bladder, but this warrants further investigation. Side effects are mainly mild to moderate, consisting primarily of paraesthesia, dizziness, nausea/vomiting, falls/balance disorders, insomnia, urinary tract infections and asthenia. Side effects are worse when administered intravenously and when administered as an immediate release compound. Serious adverse events are rarely seen in the marketed clinical dosages. In conclusion, 4-AP is easy and safe to use. Slow release 4-AP shows more robust clinical effects and a more beneficial side-effect profile than immediate release 4-AP.

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Aminopyridines for symptomatic treatment in multiple sclerosis

Cited by 65 publications

References 31 publications

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

Inhibition of Neuronal Degenerin/Epithelial Na+ Channels by the Multiple Sclerosis Drug 4-Aminopyridine

4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review

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