Antagonism of polymyxin B-induced neuromuscular and cardiovascular depression by 4-aminopyridine in the anesthetized cat

Abstract

In an attempt to find a better antidote to polymyxin B-induced neuromuscular blockade, the authors tested 4-aminopyridine, 0.4--1 mg/kg, in ten anesthetized cats. The sciatic--tibialis anterior nerve--muscle preparation was used. The neuromuscular blockade was successfully reversed in all cats. Rapidity of reversal depended on the dose of 4-aminopyridine administered. At 0.6--1 mg/kg, reversal of the twitch response from 20 per cent of control to 80 per cent of control required 2.4 (SE, 0.5) min; to 100 per cent, 14.4 (SE, 3.7) min. An overshoot of the recovery of neuromuscular blockade of 6--10 hours' duration followed the reversal. The mechanical twitch response reached a peak of approximately 140 per cent of control at 2 hours. At a lower dosage, 0.4 mg/kg, two of three cats took more than an hour for complete recovery of the twitch response, and the overshoot was approximately 10 per cent of control. The hypotensive effect of polymyxin B was partially reversed, but the bradycardia was not. It is concluded that 4-aminopyridine is an effective antidote to polymyxin B-induced neuromuscular blockade in the cat.