title: Historical overview of the rationale for the pharmacological use of prolonged-release fampridine in multiple sclerosis.
abstract: 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.
authors.affiliation: Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Spain. oscar.fernandez.sspa@juntadeandalucia.es
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernandez
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Norman
authors.initials: N
authors.lastname: Putzki
mesh_terms: D015761:4-Aminopyridine / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine