The Use of Aminopyridines in Neurological Disorders

@article{Sedehizadeh2012TheUO,
  title={The Use of Aminopyridines in Neurological Disorders},
  author={Saam Sedehizadeh and Michael Keogh and Paul Maddison},
  journal={Clinical Neuropharmacology},
  year={2012},
  volume={35},
  pages={191–200}
}
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… 
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4-Aminopyridine is a promising treatment option for patients with gain-of-function KCNA2-encephalopathy
TLDR
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
TLDR
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
TLDR
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
TLDR
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
TLDR
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.
Liver and kidney damage induced by 4-aminopyridine in a repeated dose (28 days) oral toxicity study in rats: gene expression profile of hybrid cell death.
3,4‐diaminopyridine reverses paralysis in botulinum neurotoxin‐intoxicated diaphragms through two functionally distinct mechanisms
Complete reversal of Lambert–Eaton myasthenic syndrome synaptic impairment by the combined use of a K+ channel blocker and a Ca2+ channel agonist
TLDR
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
TLDR
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.
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