The use of 4-aminopyridine (fampridine) in demyelinating disorders

4-Aminopyridine (4-AP or fampridine) is a potassium channel-blocking agent that has been shown to restore conduction in focally demyelinated axons. A sustained-release matrix tablet form of 4-AP (fampridine-SR) is currently undergoing multicenter clinical trials in patients with multiple sclerosis or chronic spinal cord injury. This review describes the pharmacology and mechanisms of action of 4-AP, its pharmacokinetics in human subjects, and the outcomes of clinical trials employing either immediate-release or sustained-release formulations of the drug. The randomized clinical trials that have been completed to date indicate that K+ channel blockade may prove to be a useful strategy for ameliorating central conduction deficits due to demyelination. Diverse neurological gains have been reported for both motor and sensory domains. At the present time, however, the clinical trials have not provided sufficiently robust or definitive evidence of efficacy to gain regulatory approval for the symptomatic management of patients with either multiple sclerosis or spinal cord injury.