4-Aminopyridine potentiates neostigmine and pyridostigmine in man.
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 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/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 per cent, 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.
D000328:Adult; D000631:Aminopyridines / Q000008:administration & dosage / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects; D010197:Pancuronium / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000494:pharmacology*
D000631:Aminopyridines; D009388:Neostigmine; D001285:Atropine; D010197:Pancuronium; D011729:Pyridostigmine Bromide