The relationship between the level of cholinesterase in plasma and the action of suxamethonium in animals.
1. The neuromuscular blocking action of suxamethonium, given by intravenous injection, and the effect upon it of iso-OMPA (tetraisopropyl pyrophosphoramide) in doses which produced marked selective inhibition of cholinesterase in blood were studied in anaesthetized rats and cats, and in mice.2. In cats experiments were also carried out in which suxamethonium was given by intravenous infusion until an effect which remained constant with time was achieved. From the degree of neuromuscular block (under equilibrium conditions) obtained with different infusion rates the infusion rate for 50% reduction in twitch tension of the indirectly stimulated soleus and gastrocnemius muscles (IR50) was calculated. The effect on it of raising the suxamethonium hydrolysing capacity of blood and of selectively reducing the level of cholinesterase in blood by various doses of iso-OMPA was then investigated.3. At relevant stages of each experiment cholinesterase activity in blood was determined with butyrylcholine or benzoylcholine and where appropriate with suxamethonium as substrate.4. The results obtained show that in rats and cats the effectiveness of suxamethonium is unrelated to the level of cholinesterase activity in blood and that raising the suxamethonium hydrolysing capacity in the blood up to 22-fold (in cats) only reduces the IR50 by a factor of 1.6.5. The enhancement of the effectiveness of suxamethonium in the three species (2- to 3-fold in rats, 2- to 4-fold in mice and 7- to 8-fold in cats under the conditions used for comparison) which follows the administration of iso-OMPA is attributable to inhibition of cholinesterase in the tissues.6. It is concluded that the results obtained clearly indicate that the species studied do not give information as regards suxamethonium and its metabolism which is applicable to man.
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001565:Benzoates; D001831:Body Temperature; D002415:Cats; D002794:Choline; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood*; D005260:Female; D007734:Kymography; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects; D010756:Phosphoric Acids / Q000494:pharmacology; D051381:Rats; D013390:Succinylcholine / Q000494:pharmacology*
D001565:Benzoates; D002800:Cholinesterase Inhibitors; D010756:Phosphoric Acids; D000110:Acetylcholinesterase; D002802:Cholinesterases; D013390:Succinylcholine; D002794:Choline