The Use of Aminopyridines in Neurological Disorders

  title={The Use of Aminopyridines in Neurological Disorders},
  author={Saam Sedehizadeh and Michael Keogh and Paul Maddison},
  journal={Clinical Neuropharmacology},
AbstractAminopyridines are members of a family of monoamino and diamino derivatives of pyridine, and their principal mechanism of action is dose-dependent blockade of voltage-gated potassium channels, in particular, fast voltage-gated potassium channels. To date, only 2 main broad-spectrum potassium channel blockers, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP), have been used as investigational new drugs in various neurological diseases. More recently, licensed versions of these… 
4-Aminopyridine is a promising treatment option for patients with gain-of-function KCNA2-encephalopathy
It is shown for KCNA2-encephalopathy that the K+ channel blocker 4-aminopyridine can antagonize gain-of-function defects caused by variants in the KV1.2 subunit in vitro, by reducing current amplitudes and negative shifts of steady-state activation and increasing the firing rate of transfected neurons.
Synaptic Pathophysiology and Treatment of Lambert-Eaton Myasthenic Syndrome
The current treatment options for LEMS patients are discussed, while also considering recent work demonstrating the therapeutic potential of GV-58 alone and in combination with 3,4-DAP.
4-Aminopyridine Improves Lower Urinary Tract Symptoms in a Patient With Benign Prostatic Hyperplasia and Downbeat Nystagmus Syndrome
This is the first clinical observation of the mode of action of 4-AP in urological symptoms in humans and a significant improvement of symptoms was observed in relation to the voided volume.
4-Aminopyridine ameliorates mobility but not disease course in an animal model of multiple sclerosis
4-aminopyridine is not just a symptomatic therapy, it has a neuroprotective effect – No
Alterations in excitability and ion channel malfunctions have been documented in various neuroinflammatory and degenerative disorders and might be associated with a variety of functional consequences, but moreover direct or indirect neuroprotective properties.
Targeting ion channels for the treatment of autoimmune neuroinflammation
The emerging knowledge about ion channels in the context of autoimmune neuroinflammation is discussed and special focus is given to those candidates that could be attractive novel targets for future therapeutic approaches in neuroimmune autoinflammation.
Complete reversal of Lambert–Eaton myasthenic syndrome synaptic impairment by the combined use of a K+ channel blocker and a Ca2+ channel agonist
GV‐58, a Ca2+ channel agonist developed from the cyclin‐dependent kinase inhibitor (R)‐roscovitine, does not significantly inhibit cell division at physiological levels of ATP and is suggested as a possible alternative treatment approach to LEMS and other neuromuscular diseases.
Inverse Modulation of Neuronal Kv12.1 and Kv11.1 Channels by 4-Aminopyridine and NS1643
Identification of currents in native cell types with mode shift that are activated through 4-AP and inhibited by NS1643 can provide strong evidence for contribution of Kv12.1-mediated currents.


The use of 4-aminopyridine (fampridine) in demyelinating disorders.
  • K. Hayes
  • Biology, Medicine
    CNS drug reviews
  • 2004
The randomized clinical trials that have been completed to date indicate that K+ channel blockade may prove to be a useful strategy for ameliorating central conduction deficits due to demyelination, but the clinical trials have not provided sufficiently robust or definitive evidence of efficacy to gain regulatory approval for the symptomatic management of patients with either multiple sclerosis or spinal cord injury.
3,4-diaminopyridine for the treatment of Lambert–Eaton myasthenic syndrome
Four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS demonstrated a significant effect on muscle strength and compound muscle action potential amplitude and this drug is the mainstay for symptomatic treatment of LEMS.
3,4-Diaminopyridine as a treatment for amyotrophic lateral sclerosis
The Therapeutic Mode of Action of 4-Aminopyridine in Cerebellar Ataxia
It is shown that, in contrast to what is commonly believed, therapeutic concentrations of 4-AP do not increase the inhibitory drive of cerebellar Purkinje cells, and instead restores the severely diminished precision of pacemaking in Purkinja cells of EA2 mutant mice by prolonging the action potential and increasing theaction potential afterhyperpolarization.
Lack of effect of 4-aminopyridine on choreic movements.
  • H. Lundh, C. Fehling
  • Medicine, Biology
    Journal of neurology, neurosurgery, and psychiatry
  • 1982
4-Aminopyridine is neuropharmacologically a very active substance enhancing several types of synaptic transmission and has been used clinically in the treatment of disorders of neuromuscular transmission and as an anticurare agent in three cases of Huntington's disease.
3,4-Diaminopyridine safety in clinical practice: an observational, retrospective cohort study
There was one case of epileptic seizure, one of hepatotoxicity and one of heart palpitations thought ‘possibly’ to be linked to 3,4-DAP, which underline the need for continued monitoring during treatment with 3, 4- DAP.
3,4-Diaminopyridine in the treatment of congenital (hereditary) myasthenia.
3,4-DAP, either alone or combined with anticholinesterase medication, may be a useful additional treatment in congenital myasthenia.
Treatment of downbeat nystagmus with 3,4-diaminopyridine
It is demonstrated that a single dose of 3,4-DAP significantly improved downbeat nystagmus (DBN) syndrome in a prospective, placebo-controlled, double-blind study with a crossover design.
Effects of 4-aminopyridine on normal and demyelinated mammalian nerve fibres
4AP is effective at lower concentrations, and is the more promising for clinical use, as it has already been used with beneficial effects in the treatment of Eaton-Lambert syndrome and myasthenia gravis.
Comparison of 10-mg Doses of 4-Aminopyridine and 3,4-Diaminopyridine for the Treatment of Downbeat Nystagmus
  • R. Kalla, R. Spiegel, M. Strupp
  • Medicine
    Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
  • 2011
10-mg doses of 4-AP lead to a more pronounced decrease of the SPV of downbeat nystagmus than do equivalent doses of 3,4-DAP.