Historical overview of the rationale for the pharmacological use of prolonged-release fampridine in multiple sclerosis.

Multiple sclerosis is a progressive demyelinating neurological disease resulting in long-term disability, commonly manifesting in walking impairment and reduced quality of life. The use of the potassium channel blocker fampridine, chemically 4-aminopyridine, as an immediate-release formulation to improve action potential conduction in demyelinated axons was hampered by adverse events, including seizures. The prolonged-release formulation of fampridine (known as modified- or sustained-release fampridine in some countries and dalfampridine extended release in the USA) has a longer apparent half-life and a lower peak plasma concentration versus immediate-release fampridine formulations, sustaining its duration of action and reducing the incidence of adverse events. Prolonged-release fampridine is the first drug specifically licensed to improve walking in patients with multiple sclerosis, and has been shown to consistently improve walking ability in a third of patients. Prolonged-release fampridine Timed-Walk Responders showed both clinically significant improvements in walking speed and in patient-reported walking ability.