Mechaism of neuromuscular blockade with some antiepileptic drugs

Effects of four antiepileptic drugs, viz., diphenylhydantoin, trimethadione, phenobarbitone and ethosuximide, were studied on different in vitro and in vivo skeletal muscle preparations which consisted of frog rectus, rat phrenic nerve diaphragm and cat gastrocnemius sciatic nerve preparations. A dose related blockade of neuromuscular transmission was seen with all the compounds tested. The blockade was mainly confined to the neuromuscular junction, although direct stimulation of muscle was slightly affected. The blockade was partially antagonized by physostigmine, adrenaline, succinylcholine, choline, tetraethylammonium and KCl and was additive to that due to tubocurarine. Moreover, the drugs were found to possess moderate local anaesthetic activity. The blockade was therefore considered to be partly due to curariform activity and partly due to their local anaesthetic activity.