Cholinesterase inhibitors do not prolong neuromuscular block produced by mivacurium

Cholinesterase inhibitors antagonize neuromuscular block produced by mivacurium, but some may also decrease its metabolism by inhibiting pseudocholinesterase. These opposing interactions were examined in rats anaesthetized with pentobarbitone. After spontaneous recovery from an initial bolus dose of 0.03 mg kg-1, mivacurium was infused to produce 80-90% block of gastrocnemius muscle twitch. After 15 min, the infusion was discontinued and saline, edrophonium, pyridostigmine or neostigmine was administered. Fifteen minutes later, a second bolus dose of mivacurium was given. Edrophonium, pyridostigmine and neostigmine reduced the subsequent maximum block, compared with the change in saline control, by 3%, 19% and 35%, respectively. Correspondingly, the time to recovery of T1 to 50% was decreased by 20%, 58% and 62%. In rats, acetylcholinesterase-mediated antagonism of neuromuscular block predominated over decreased pseudocholinesterase-mediated metabolism, such that prior administration of a cholinesterase inhibitor did not prolong the neuromuscular blocking effects of mivacurium.