Relative importance of the enzymic hydrolysis of sexamethonium in plasma and tissues: studies in Rhesus monkeys.

Abstract

1. Suxamethonium was given by intravenous infusion to anaesthetized Rhesus monkeys and the infusion rate required to produce after 10 min a 50% reduction in twitch tension of the indirectly stimulated gastrocnemius or tibialis anterior muscle (IR50) was calculated from results obtained with paired infusions of two concentrations, repeated at intervals. The IR50 values in three monkeys were (388, 958 and 1,010 nmol/kg)/minute.2. In one experiment the cholinesterase activity in plasma was increased to 125 and then to 182% of the initial value by infusions of purified human cholinesterase (usual enzyme). This increased the IR50 by 34 and then by 60%, respectively.3. Inhibition by iso-OMPA of cholinesterase activity in plasma and tissues (four monkeys) by more than 90% lowered the mean IR50 value to (69 +/- 11 (S.E.M.) nmol/kg)/minute. Restoration of cholinesterase activity in the plasma of these animals by infusion of purified human cholinesterase raised the IR50's to values within the normal range.4. It is concluded that in the Rhesus monkey most of the infused suxamethonium is hydrolyzed by the cholinesterase in plasma before reaching the motor endplates. This agrees with observations in man with usual cholinesterase and contrasts with experiments in the cat where the hydrolysis of suxamethonium by cholinesterase in tissues was found to be more important than the hydrolysis by cholinesterase in plasma.