Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo.

Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE

Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.

Organophosphate Poisoning*; Acetylcholinesterase/*blood ; Acetylcholinesterase/*metabolism ; Cholinesterase Reactivators/*pharmacology ; Enzyme Activation/*drug effects ; Oximes/*pharmacology ; Pyridinium Compounds/*pharmacology ; Trimedoxime/*pharmacology; Animals ; Central Nervous System/drug effects ; Central Nervous System/enzymology ; Central Nervous System/metabolism ; Cholinesterase Reactivators/administration & dosage ; Drug Therapy, Combination ; Female ; Organophosphates ; Oximes/administration & dosage ; Pyridinium Compounds/administration & dosage ; Rats ; Rats, Wistar ; Trimedoxime/administration & dosage

Up to now, intensive attempts to synthesize a universal reactivator able to reactivate cholinesterases inhibited by all types of nerve agents/organophosphates were not successful. Therefore, another approach using a combination of two reactivators differently reactivating enzyme was used: in rats poisoned with tabun and treated with combination of atropine (fixed dose) and different doses of trimedoxime and HI-6, changes of acetylcholinesterase activities (blood, diaphragm and different parts of the brain) were studied. An increase of AChE activity was observed following trimedoxime treatment depending on its dose; HI-6 had very low effect. Combination of both oximes showed potentiation of their reactivation efficacy; this potentiation was expressed for peripheral AChE (blood, diaphragm) and some parts of the brain (pontomedullar area, frontal cortex); AChE in the basal ganglia was relatively resistant. These observations suggest that the action of combination of oximes in vivo is different from that observed in vitro.
(Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

0 (Cholinesterase Reactivators)
0 (Organophosphates)
0 (Oximes)
0 (Pyridinium Compounds)
56-97-3 (Trimedoxime)
EC 3.1.1.7 (Acetylcholinesterase)
HUV88P6SJS (asoxime chloride)
S45M750QSH (tabun)

Date Created: 20100220 Date Completed: 20100901 Latest Revision: 20151119

20231215

10.1016/j.cbi.2010.02.009

20167212