Inhibition of True Cholinesterase in TOCP Poisoning with Potentiation by ‘Tween 80’

Abstract

SINCE the work of Earl and Thompson^1,2 on hens, and the brief note by Mendel and Rudney³ on rats, it has often been accepted^4,5 that in tri-ortho cresyl phosphate (TOCP) intoxication, pseudocholinesterase is markedly inhibited but that there is little or no decrease in true cholinesterase. A decrease in red blood cell cholinesterase has, however, been reported in rabbits⁶ and a slight fall in man⁷ after treatment with TOCP by mouth, and Taylor⁸ has commented on parasympathomimetic effects in cats injected with this compound. I have investigated changes in cholinesterase in baboons after oral doses of TOCP. Monkeys have been found to be very resistant to TOCP by mouth^9,10 and it has been suggested the monkeys do not absorb it from the gut. In addition to pure TOCP therefore a 10 per cent emulsion in 10 per cent ’Tween 80‘ has also been tried in the present work at the suggestion of Dr J. D. Taylor of the Department of Pharmacology, University of Alberta. He has found this emulsion more active than the pure substance (personal communication from J. D. Taylor). The results to be described show that after administration of either preparation to the baboon, pseudocholinesterase is very readily inhibited, but that marked inhibition of true cholinesterase also occurs. In the reports of TOCP poisoning in man after accidental ingestion, diarrhoea and abdominal pain have often been noted and have sometimes been severe¹¹. These effects would be expected to accompany inhibition of true cholinesterase.