title: The site of action of trimethaphan-induced neuromuscular blockade in isolated rat and frog muscle.
abstract: 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.
mesh_terms: D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000294:innervation; D009388:Neostigmine / Q000494:pharmacology; D009466:Neuromuscular Blocking Agents; D011892:Rana catesbeiana; D051381:Rats; D011919:Rats, Inbred Strains; D014294:Trimethaphan / Q000494:pharmacology*; D014403:Tubocurarine / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D002038:Bungarotoxins; D006584:Hexamethonium Compounds; D009466:Neuromuscular Blocking Agents; D009388:Neostigmine; D018738:Hexamethonium; D002110:Caffeine; D014294:Trimethaphan; D002217:Carbachol; D014403:Tubocurarine