The site of action of trimethaphan-induced neuromuscular blockade in isolated rat and frog muscle.

The present study was undertaken to determine the site of action of trimethaphan in causing neuromuscular blockade using isolated rat and frog muscle. Trimethaphan and d-tubocurarine attenuated the twitch tension developed by nerve stimulation, trimethaphan being 1/100 to 1/200 as potent as d-tubocurarine. Neostigmine potentiated the inhibitory effect of trimethaphan but reversed the effect of d-tubocurarine. Trimethaphan shifted the dose response curve of frog rectus abdominis muscle for carbachol downwards, while d-tubocurarine shifted the curve parallel to the right. Treatment with d-tubocurarine or succinylcholine protected acetylcholine receptors from persistent blockade by alpha-bungarotoxin while, in contrast, trimethaphan failed to protect the receptors. The findings indicate that trimethaphan acts on the motor endplate but, unlike d-tubocurarine, does not interact with the recognition site of acetylcholine receptors; the action of trimethaphan appears to be associated with the blockade of endplate ionic channels.