Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin and beta-bungarotoxin

Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch ("facilitation") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane.