Protection by a carbamate against inactivation of cholinesterase and against the induction of supersensitivity of the ileum to acetylcholine produced by repeated administration of an organophosphate
Hayashi, E.; Okudaira, H.; Yamada, S.
Toxicology and Applied Pharmacology 48(1 Part 1): 111-116
1979
ISSN/ISBN: 0041-008X PMID: 452034 Document Number: 141455
The effects of repeated administration of the insecticide propaphos (an organophosphorus cholinesterase inhibitor) and 2-s-butylphenyl-n-methylcarbamate (BPMC, a carbamate cholinesterase inhibitor) on the pharmacological responsiveness of the ileum and on the cholinesterase activity in blood and tissues were investigated in guinea pigs. Propaphos (3.3 .times. 10-7 M) and BPMC (4.8 .times. 10-6 M) each inhibited the cholinesterase activity in blood in vitro and enhanced the contractile response of guinea pig isolated ileum to acetylcholine (ACh). After repeated administration of a sublethal dose (5 mg/kg per day pre os (p.o.)) of propaphos to guinea pigs for 7 days, the contractile response of isolated ileum to ACh (1.7 .times. 10-8-1.7 .times. 10-5 M) was markedly increased and the values of ED50 and ED80 [80% effective dose] for ACh-induced contraction significantly decreased. Since the activity of cholineseterase in the ileum was markedly reduced in these animals, the depression of the enzyme may be the major factor underlying the observed supersensitivity to ACh. The propaphos-induced supersensitivity to ACh was significantly reduced by pretreatment with sublethal doses (25 mg/kg per day p.o., 7 days) of BPMC. BPMC blocked a fraction of the inactivation of cholinesterase produced by propaphos acting in vivo on blood, brain and ileum. The BPMC-induced protection of cholinesterase might explain the mechanism by which the carbamate antagonizes the development of supersensitivity of the ileum to ACh following the administration of propaphos.