PROTECTION BY A CARBAMATE AGAINST INACTIVATION OF CHOLINESTERASE AND AGAINST THE INDUCTION OF SUPER-SENSITIVITY OF THE ILEUM TO ACETYLCHOLINE PRODUCED BY REPEATED ADMINISTRATION OF AN ORGANOPHOSPHATE

The effects of repeated administration of propaphos (an organophosphorus cholinesterase inhibitor) and 2-sec-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 × 10-7 m) and BPMC (4.8 × 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/day po) of propaphos to guinea pigs for 7 days, the contractile response of isolated ileum to ACh (1.7 × 10-8-1.7 × 10-5 m) was markedly increased and the values of ED50 and ED80 for ACh-induced contraction significantly decreased. Since the activity of cholinesterase 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/day po, 7 days) of BPMC. In addition BPMC blocked a fraction of the inactivation of cholinesterase produced by propaphos acting in vivo on blood, brain, and ileum. Therefore it is possible that 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. © 1979 Academic Press, Inc. All rights reserved.