Factors limiting the rate of termination of the neuromuscular blocking action of fazadinium dibromide

Abstract

1 Reasons for the termination of the neuromuscular blocking action of fazadinium dibromide have been investigated. 2 In the anaesthetized cat, maximum neuromuscular block of tibialis anterior muscle twitches following rapid intravenous injection of fazadinium was obtained as the injection bolus passed through the muscle, indicating the fazadinium very readily crosses capillary membranes. 3. The half-life of plasma clearance of fazadinium was about 1 min in both cat and man, despite a 10 fold difference in duration of action in these species. Plasma samples were bioassayed for neuromuscular blocking activity on an isolated, superfused phrenic nerve-diaphragm preparation of the rat. 4 In the anaesthetized cat, occlusion of the renal or hepatic circulations did not prolong the neuromuscular blocking action of single doses of fazadinium. Repeated doses accumulated slowly when the hepatic circulation was occluded but not when the renal circulation was occluded. 5 Fazadinium is eliminated from the body by both the liver and kidneys but the rates of these processes are insufficient to account for the initial rapid plasma clearance. 6 The rate-limiting step for the termination of the neuromuscular blocking action of fazadinium is most likely to be the rate of drug-receptor dissociation