title: A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pre-treatment of soman-poisoned mice.
abstract: The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50)  value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre-treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising.
authors: Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
authors: Jiri
authors: J
authors: Kassa
authors: Kamil
authors: K
authors: Musilek
authors: Marketa
authors: M
authors: Koomlova
authors: Jiri
authors: J
authors: Bajgar
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010091:Oximes / Q000008:administration & dosage / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000494:pharmacology; D012999:Soman / Q000008:administration & dosage / Q000506:poisoning*
chemical_list: C573830:1,10-bis(pyridinium)decane; C573831:1,8-bis(4-tert-butylpyridinium)oct-1,8-diyl; C573829:1,8-bis(isoquinolinium)-oct-1,8-diyl; D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D007546:Isoquinolines; D010091:Oximes; D011726:Pyridinium Compounds; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; D011729:Pyridostigmine Bromide