Lenina_2020_Sci.Rep_10_16611

Reference

Title : Slow-binding reversible inhibitor of acetylcholinesterase with long-lasting action for prophylaxis of organophosphate poisoning - Lenina_2020_Sci.Rep_10_16611
Author(s) : Lenina OA , Zueva IV , Zobov VV , Semenov VE , Masson P , Petrov KA
Ref : Sci Rep , 10 :16611 , 2020
Abstract : Organophosphorus (OP) compounds represent a serious health hazard worldwide. The dominant mechanism of their action results from covalent inhibition of acetylcholinesterase (AChE). Standard therapy of acute OP poisoning is partially effective. However, prophylactic administration of reversible or pseudo-irreversible AChE inhibitors before OP exposure increases the efficiency of standard therapy. The purpose of the study was to test the duration of the protective effect of a slow-binding reversible AChE inhibitor (C547) in a mouse model against acute exposure to paraoxon (POX). It was shown that the rate of inhibition of AChE by POX in vitro after pre-inhibition with C547 was several times lower than without C547. Ex vivo pre-incubation of mouse diaphragm with C547 significantly prevented the POX-induced muscle weakness. Then it was shown that pre-treatment of mice with C547 at the dose of 0.01 mg/kg significantly increased survival after poisoning by 2xLD(50) POX. The duration of the pre-treatment was effective up to 96 h, whereas currently used drug for pre-exposure treatment, pyridostigmine at a dose of 0.15 mg/kg was effective less than 24 h. Thus, long-lasting slow-binding reversible AChE inhibitors can be considered as new potential drugs to increase the duration of pre-exposure treatment of OP poisoning.
ESTHER : Lenina_2020_Sci.Rep_10_16611
PubMedSearch : Lenina_2020_Sci.Rep_10_16611
PubMedID: 33024231

Related information

Inhibitor C-547

Citations formats

Lenina OA, Zueva IV, Zobov VV, Semenov VE, Masson P, Petrov KA (2020)
Slow-binding reversible inhibitor of acetylcholinesterase with long-lasting action for prophylaxis of organophosphate poisoning
Sci Rep 10 :16611

Lenina OA, Zueva IV, Zobov VV, Semenov VE, Masson P, Petrov KA (2020)
Sci Rep 10 :16611