The site of the neuromuscular block produced by polymyxin B and rolitetracycline

The site of neuromuscular blockade induced by polymyxin B and rolitetracycline was studied on isolated nerve and nerve–muscle preparations. Polymyxin B (1.8 × 10−4 M) was equipotent to lidocaine as a local anaesthetic on a frog desheathed nerve preparation, while rolitetracycline (up to 3.6 × 10−3 M) had no local anaesthetic effect. Polymyxin B (6 × 10−5 M) and rolitetracycline (7 × 10−4 M) blocked by 50% the response of rat diaphragm induced by phrenic nerve stimulation, but did not decrease the amount of acetylcholine (ACh) released from this preparation during nerve stimulation. Both antibiotics depressed the response of the rat diaphragm to inject ACh, and this response was more sensitive to inhibition by the drugs than was the response to nerve stimulation. With rolitetracycline, a concentration that blocked the response to nerve stimulation by 50% inhibited the response to injected ACh by 85%, and this relationship was similar to that with d-tubocurarine; however, polymyxin B was relatively more effective than d-tubocurarine in inhibiting the effect of ACh. Polymyxin B (1–1.5 × 10−4 M) but not rolitetracycline (1 × 10−3 M) depressed the response of the diaphragm to direct muscle stimulation. It is concluded that polymyxin B and rolitetracycline block neuromuscular transmission predominantly by an effect to depress the muscle's sensitivity to ACh; polymyxin B probably acts by an effect similar to that of local anaesthetics, while rolitetracycline probably acts by an effect similar to that of d-tubocurarinc.