The Use of Aminopyridines in Neurological Disorders

Abstract

Aminopyridines 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 compounds including dalfampridine extended release (Fampyra, Biogen Idec) for the improvement of walking in adult patients with multiple sclerosis, and amifampridine (Firdapse, Biomarin Europe Ltd) for the treatment of Lambert-Eaton myasthenic syndrome have been released, and the costs associated with using these new products highlights the importance of evaluating the clinically meaningful treatment effects of these drugs.The current review summarizes the evidence of aminopyridine use in neurological conditions and in particular presents a systematic review of all randomized trials of 3,4-DAP in Lambert-Eaton myasthenic syndrome to determine the efficacy of this treatment using meta-analysis of clinical and electrophysiological end points.

CHAPTER 6. The Molecular Diversity of Conoidean Venom Peptides and their Targets: From Basic Research to Therapeutic Applications

“…Even non-selective K V channel antagonists, such as 4-aminopyridine, are used clinically for multiple sclerosis and several other neurological diseases 91,92 (reviewed in ref. 93). The subtype-selective K V channel antagonists found in venoms are expected to provide greater therapeutic benets with fewer side effects.…”

4-Aminopyridine Does Not Enhance Flocculus Function in Tottering, a Mouse Model of Vestibulocerebellar Dysfunction and Ataxia

“…Long used experimentally to pharmacologically dissect the contributors to net ionic currents of neurons, the aminopyridines have also found several medical applications, including restoring the function of the neuromuscular junction in the paraneoplastic condition Lambert-Eaton myasthenic syndrome and improving action potential conduction through axons whose myelin has been damaged by multiple sclerosis [3]–[5]. More recently, the aminopyridines have been used to treat abnormal motor function caused by disorders of the cerebellum, with particular emphasis on the eye movement abnormalities attributable to dysfunction of the vestibulocerebellum [6].…”

Symptomatic therapy in multiple sclerosis: Big pharma should do more—YES

“…Dalfampiridine for a modest effect on gait, 3,4 botulinium A-toxin for neurogenic bladder dysfunction 5,6 and the synthetic cannabinoids for spasticity. 7 9 But their official approval will require proper trials. The use and indications for botulinum-A toxin for neurogenic detrusor overactivity and detrusor-sphincter dyssynergia is not limited only to MS, but has been approved for neurogenic bladder dysfunction secondary to spinal cord injuries and other related disorders.…”