A comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator KR-22934 with the oxime K203 and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice.
ABSTRACT The potency of bispyridinium acetylcholinesterase reactivator KR-22934 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with the oxime K203 and commonly used oximes. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of KR-22934 was slightly higher than the reactivating efficacy of K203 and roughly corresponded to the reactivating efficacy of obidoxime and trimedoxime in blood and diaphragm. On the other hand, the oxime KR-22934 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied approximately corresponded to their reactivating efficacy. Based on the results, one can conclude that the oxime KR-22934 is not suitable for the replacement of commonly used oximes for the antidotal treatment of tabun poisoning in spite of its potency to reactivate tabun-inhibited acetylcholinesterase in the peripheral compartment (blood, diaphragm).
Article: Organophosphate poisoning.[Show abstract] [Hide abstract]
ABSTRACT: The present review discusses the structure of the anticholinesterase organophosphates (OPs), which are used predominantly as insecticides. OP poisoning can occur in a variety of situations and can be accidental or suicidal. It is common in developing countries. The cholinergic syndrome is caused by acetylcholinesterase inhibition, and diagnosis is based on the clinical signs and symptoms as well as the measurement of inhibition of erythrocyte acetylcholinesterase and/or plasma cholinesterase activity. Antidotal treatment is with atropine, an enzyme reactivator such as pralidoxime and diazepam. Anticholinesterase OPs may produce effects other than the acute cholinergic syndrome, including the intermediate syndrome. Later effects may include organophosphorus-induced delayed neuropathy. Certain OPs are exploited for their anticholinesterase effects, including defoliants such as 'DEF', herbicides such as glyphosate, fire retardants and industrial intermediates. The toxicology of this group is heterogeneous and they may or may not possess anticholinesterase activity.Pharmacology [?] Therapeutics 02/1993; 58(1):51-66. · 7.75 Impact Factor
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ABSTRACT: The purpose of this study was to compare the therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-(2-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium )-2-butene dibromide), with presently used oximes (pralidoxime, obidoxime, methoxime) and H-oximes (HI-6, HLö-7) by in vitro and in vivo methods. In vitro, methoxime seems to be the most efficacious reactivator of GF agent-inhibited acetylcholinesterase because the phosphorylation of acetylcholinesterase by GF agent markedly increases its affinity for the enzyme. The oxime BI-6 is more efficacious than other presently used oximes (pralidoxime, obidoxime) but its reactivating efficacy does not reach the efficacy of H-oximes tested. On the other hand, obidoxime and pralidoxime appear to be very poor reactivators of GF agent-inhibited acetylcholinesterase because the phosphonylation of acetylcholinesterase by GF agent markedly decreases their affinity to the enzyme. In vivo, H oximes (HI-6, HLö-7) are the most efficacious antidotes for the treatment of acute poisoning with GF agent in rats while the presently used oximes such as pralidoxime and obidoxime are practically ineffective. BI-6 and methoxime are more efficacious than pralidoxime and obidoxime, nevertheless their therapeutic efficacy does not reach the efficacy of H oximes. Our results show that the ability of oximes to reactivate GF agent-inhibited acetylcholinesterase in vitro usually corresponds to their therapeutic effects against GF agent in vivo.Pharmacology & Toxicology 02/1999; 84(1):41-5.
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ABSTRACT: The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6(1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium+ ++/-2-butene dibromide), against the organophosphate soman was compared with oximes at present used (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) using in vitro and in vivo methods. H oximes HI-6 and HLö-7 seem to be the most efficacious acetylcholinesterase reactivators against soman according to the evaluation of their reactivating and therapeutic efficacy in vitro as well as in vivo. The new oxime BI-6 is not as effective as the H oximes against soman, nevertheless it is significantly more effective against soman than the currently available oximes, pralidoxime, obidoxime and methoxime, which failed to protect rats poisoned with supralethal doses of soman. Our results confirm that the reactivating efficacy of oximes evaluated by the methods in vitro closely correlates not only with the potency of oximes in vivo in reactivating soman-inhibited acetylcholinesterase but also with the ability to protect rats poisoned with supralethal doses of soman.Toxicology 03/1999; 132(2-3):111-8. · 3.75 Impact Factor