Enhancing neural transmission in multiple sclerosis (4-aminopyridine therapy).

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Goodman AD, Stone RT

Enhancing neural transmission in multiple sclerosis (4-aminopyridine therapy).

Neurotherapeutics. 2013 Jan;10(1):106-10. doi: 10.1007/s13311-012-0156-3.

PubMed ID

23184313 [ View in PubMed

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Abstract

Enhancing neural transmission by improving axonal conduction and synaptic neurotransmitter release is a novel strategy to improve symptoms in multiple sclerosis. Dalfampridine (4-aminopyridine extended-release) is a first-in-class medication that targets the damaged nervous system through blockage of voltage-gated potassium channels. Through a series of clinical trials, dalfampridine (dosed at 10 mg twice daily) has been found to improve walking speed by approximately 25 % on average in one third of individuals with multiple sclerosis regardless of disease stage. Furthermore, it significantly improves patients' perception of their ambulatory disability and may improve lower extremity strength. Given the mechanism of action, the most serious adverse effect is its pro-convulsant property, which occurs more frequently at high serum concentrations. The most common adverse events include increased falls, urinary tract infections, dizziness, insomnia, and headaches. Despite these potential side-effects, the vast majority of individuals who derive benefit continue on the treatment. The exact mechanism of action is uncertain, as is the reason for response variability. The medication serves as proof-of-concept that targeting axonal transmission can improve disability in multiple sclerosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dalfampridine	Potassium voltage-gated channel subfamily D member 2	Protein	Humans	Yes	Antagonist	Details