The interaction between d-tubocurarine, pancuronium, polymyxin B, and neostigmine on neuromuscular function

The interaction between pancuronium, d-tubocurarine, polymyxin B, and neostigmine was studied in the rat diaphragm-phrenic nerve preparation. Polymyxin B (5 mug/ml) did not affect twitch tension alone but decreased the pancuronium ED50 from 0.8 mug/ml to 0.32 mug/ml and the d-tubocurarine ED50 from 0.25 mug/ml to 0.15 mug/ml. Neostigmine (0.2 to 10 mug/ml) antagonized pancuronium or d-tubocurarine-induced depression of twitch tension. In contrast, neostigmine (0.001 to 0.2 mug/ml) augmented polymyxin B depression. Similarly, neostigmine (0.1 mug/ml) augmented combined polymyxin B-pancuronium or polymyxin B-d-tubocurarine depression of twitch tension. The authors conclude that polymyxin B potentiates the neuromuscular blockade from pancuronium or d-tubocurarine and that neostigmine further augments this block.