Potentiation of neostigmine and pyridostigmine by 4-aminopyridine in the rat

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Abstract
The interaction between 4-aminopyridine and neostigmine or pyridostigmine was studied in vivo in the rat sciatic nerve-anterior tibialis preparation using the constant infusion of pancuronium technique. The ED50 (dose of drug which produced a 50% antagonism) of neostigmine, pyridostigmine and 4-aminopyridine were 18, 49 and 440 μg kg−1 respectively. The addition of 100 μg kg−1 of 4-aminopyridine, which produced no antagonism by itself, decreased the neostigmine ED50 to 7·4 μg kg−1. The addition of 200 μg kg−1 of 4-aminopyridine, which produced a 30% antagonism by itself, decreased the ED50 of pyridostigmine to 11 μg kg−1. We conclude that both neostigmine and pyridostigmine interact with 4-amino-pyrine synergistically.