The evaluation of prophylactic efficacy of newly developed reversible inhibitors of acetylcholinesterase in soman-poisoned mice - a comparison with commonly used pyridostigmine.
The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC-37, PC-48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman-induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising.
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
Jiri
J
Kassa
Jan
J
Korabecny
Vendula
V
Sepsova
Martina
M
Tumova
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010879:Piperazines / Q000627:therapeutic use*; D011729:Pyridostigmine Bromide / Q000627:therapeutic use*; D012999:Soman / Q000037:antagonists & inhibitors / Q000506:poisoning*; D013619:Tacrine / Q000031:analogs & derivatives* / Q000627:therapeutic use
C000599736:7-methoxy-N-(2-(4-(3-methylbenzyl)piperazine-1-yl)ethyl)-1,2,3,4-tetrahydroacridin-9-amine; D000931:Antidotes; D002800:Cholinesterase Inhibitors; C000599737:N-(2-(4-(3-bromobenzyl)piperazine-1-yl)ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine; C000599738:N-ethyltacrine; C000599739:N-hexyl-7-methoxytacrine; D010879:Piperazines; D013619:Tacrine; D012999:Soman; D011729:Pyridostigmine Bromide