Mechanism of action
4-Aminopyridine (4-AP) is a voltage-gated, fast potassium channel blocker capable of improving axonal conduction by facilitating the propagation of action potentials in demyelinated nerve fibers.84
Preclinical trials of orally administered 4-AP found transient improvements in neurologic function in patients with long-standing spinal cord injury.86 Administration of 4-AP led to marked and sustained reductions in upper- or lower-extremity spasticity due to cervical cord lesions. Other clinical benefits included:86
Segal et al.84 studied long-term safety and efficacy of orally administrated, immediate-release 4-AP. They found that patients given 30 mg per day over a period of 3 months displayed improvement and recovery of sensory and motor function and diminished spasticity. (Patients receiving 6 mg per day did not benefit.)
Other investigations of 4-AP in patients with spinal cord injury report enhanced gait,87 improved motor control and sensory ability below the injury site, and reduction in chronic pain and spasticity.88
One study using intravenous 4-AP to treat pain and spasticity in spinal cord injury found that benefits did not outweigh adverse effects.89
4-AP is well absorbed and reaches peak concentrations in 2 to 4 hours.85
No recommended dosage has been set, since 4-AP is not approved by the U.S. Food and Drug Administration. A dosage of 10 mg two or three times daily has been used in studies.
Experimental studies and clinical observations have documented epileptogenic effects. Application of 4-AP on hippocampal slices produced several patterns of epileptiform discharges and seizurelike events.90 In studies of 4-AP to treat spinal cord injury in rats, all animals that received a dose of 6 mg/kg had generalized seizures.7 New onset of seizures can complicate 4-AP therapy.91
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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