4-Aminopyridine potentiates neostigmine and pyridostigmine in man

Abstract

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 ± 6% (peak)antagonism. The dose that produced 50% antagonism (ED50) of neostigmine alone was 22μg/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 μg/kg. The ED50 of pyridostigmine alone was 110 μg/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 μg/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevents a change in heart rate by 68 and 70%, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.