Efficacy and Safety of 4‐Aminopyridine in Patients with Long‐Term Spinal Cord Injury: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Grijalva, Israel; Guı́zar-Sahagún, Gabriel; Castañeda‐Hernández, Gilberto; Mino, D; Maldonado-Julián, Héctor; Vidal‐Cantú, Guadalupe C.; Ibarra, Antonio; Serra, Omar; Salgado–Ceballos, Hermelinda; Arenas-Hernández, Rita

doi:10.1592/phco.23.7.823.32731

Cited by 49 publications

(35 citation statements)

References 51 publications

(101 reference statements)

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“…[46,47] , including the 2 recently completed Phase III studies [47] . Nevertheless, two 4-AP trials have found statistically significant improvements in functional recovery [48,49] , suggesting that potassium channel blockade is still a viable mechanism for potentially restoring signal conduction in patients with spinal cord injury.…”

Section: Change Of Refractoriness In 4-ap-mediated Axonal Conduction mentioning

confidence: 99%

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Shi

Sun

2011

Neurosci. Bull.

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Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. Myelin disruption resulting from trauma and biochemical reaction is a common pathological event in spinal cord injury and chronic neurodegenerative diseases. Myelin damage-induced axonal conduction block is considered to be a significant contributor to the devastating neurological deficits resulting from trauma and illness. Potassium channels are believed to play an important role in axonal conduction failure in spinal cord injury and multiple sclerosis. Myelin damage has been shown to unmask potassium channels, creating aberrant potassium currents that inhibit conduction. Potassium channel blockade reduces this ionic leakage and improves conduction. The present review was mainly focused on the development of this technique of restoring axonal conduction and neurological function of demyelinated axons. The drug 4-aminopyridine has recently shown clinical success in treating multiple sclerosis symptoms. Further translational research has also identified several novel potassium channel blockers that may prove effective in restoring axonal conduction.

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Section: Change Of Refractoriness In 4-ap-mediated Axonal Conduction mentioning

confidence: 99%

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Shi

Sun

2011

Neurosci. Bull.

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“…Unfortunately, research regarding its efficacy in SCI has been inconclusive. Although animal models and some early studies reported improvement in function and sensation, subsequent randomized, placebo-controlled studies have not demonstrated clinically significant benefits [16][17][18][19][20][21][22]. Summative interpretation of these results is difficult due to small numbers, mixed patient populations and variations in duration, dosage, and mechanism of administration.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…The known side effects of 4-aminopyridine include peripheral vasospasm, dizziness, nausea, gastritis, paresthesia and thrombocytopenia. 41 High doses can cause convulsions. The drug has an orphan drug status for multiple sclerosis in the United States and has undergone phase III clinical studies for this disease.…”

Section: -Aminopyridine (Fampridine)mentioning

confidence: 99%

“…It should be mentioned that earlier reports from clinical trials with smaller numbers of subjects had found more encouraging results with the use of this drug in chronic, incomplete SCI: they had reported significant improvements in motor and sensory functions. 41 Riluzole. Riluzole is a sodium channel blocker with antiexcitotoxic effects, already registered for the treatment of amiotrophic lateral sclerosis.…”

Section: -Aminopyridine (Fampridine)mentioning

confidence: 99%

A review of published reports on neuroprotection in spinal cord injury

et al. 2009

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Study design: Literature review. Objectives: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). Setting: This paper is the result of a collaboration between a group of European scientists. Methods: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. Results: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/ re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'g-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin geneFincluding neurotransmitterFreceptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. Conclusion: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.

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Efficacy and Safety of 4‐Aminopyridine in Patients with Long‐Term Spinal Cord Injury: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Cited by 49 publications

References 51 publications

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons

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

A review of published reports on neuroprotection in spinal cord injury

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