Antagonism of Org NC 45 neuromuscular blockade by neostigmine, pyridostigmine, and 4-aminopyridine.

The antagonism of Org NC 45 neuromuscular blockade by neostigmine, pyridostigmine, 4-aminopyridine, and their combinations was studied in the in vivo rat sciatic nerve anterior tibialis preparation using the constant infusion of Org NC 45 technique. The ED50 (dose of drug which produced a 50% antagonism) of neostigmine, pyridostigmine, and 4-aminopyridine were 14.5, 75, and 466 micrograms/kg, respectively. The addition of 100 microgram/kg of 4-aminopyridine, which produced no antagonism by itself, decreased neostigmine ED50 to 9.8 micrograms/kg. The addition of 200 micrograms/kg of 4-aminopyridine, which produced a 14.8% antagonism by itself, decreased the ED50 of pyridostigmine to 17.5 micrograms/kg. We concluded that neostigmine, pyridostigmine, and 4-aminopyridine effectively antagonize an Org NC 45 neuromuscular blockade. Neostigmine and pyridostigmine interact with 4-aminopyridine in a synergistic manner. The doses of antagonists were very similar to those required to antagonize a pancuronium neuromuscular blockade.