4-Aminopyridine Potentiates Neostigmine and Pyridostigmine in Man

Abstract

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, 57 anesthetized surgical patients were studied using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism but 0.5 mg/kg produced a mean 24 .+-. 6% (peak) antagonism. The dose that produced 50% antagonism (ED50) of neostigmine alone was 22 .mu.g/kg; with 0.35 mg/kg 4-aminopyridine it was 7 .mu.g/kg. The ED50 of pyridostigmine alone was 110 .mu.g/kg; with 0.35 mg/kg 4-aminopyridine it was 27 .mu.g/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 prevent a change in heart rate by 68 and 70%, respectively. Apparently 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.