a-Aminopyridine

Abstract Aminopyridines block voltage-activated potassium channels, thereby increasing action potential duration (6) and neurotransmitter release. They have been used with moderate success in the treatment of multiple sclerosis (4, 17) and Lambert-Eaton myasthenic syndrome (15). The most serious side effects are generalized seizures (4). Cardiac arrhythmias (5) and gastrointestinal symptoms also occur (1). 4-Aminopyridine is an organic base and exists in both charged and uncharged forms in aqueous solution (12). 3,4-Diaminopyridine has approximately 40 times the blocking potency of 4-aminopyridine (16); however, 4-aminopyri dine is more lipid-soluble than 3,4-diaminopyridine and, therefore, more readily crosses the blood-brain barrier (14). High-performance liquid chromatography methods for de termination of 4-aminopyridine in tissue samples and plasma are available (7,20). Treatment of rats in vivo with 5 mg/kg of 4-aminopyri dine induces generalized convulsions in 74% of the animals and death in 13% (11). Epileptiform discharges upon ap plication of 4-aminopyridine occur in hippocampal slice preparations (2).