Most cited article - PubMed ID 16838488
Syntéza reaktivátorů fosforylované acetylcholinesterasy bis-pyridiniumdialdoximového typu s 3-oxapentanovým spojovacím retezcem a jejich testování in vitro na modelu enzymu inhibovaného chlorpyrifosem a methylchlorpyrifosem
[Synthesis of reactivators of phosphorylated acetylcholinesterase of bis-pyridiniumdialdoxime type with a 3-oxapentane connecting chain and their testing in vitro on a model of the enzyme inhibited by chlorpyrifos and methylchlorpyrifos]
The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 microg/kg i.m.; 80% of LD(50) value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 24 h following tabun challenge while one tabun-poisoned rats died within 24 h after tabun poisoning when the rats were treated with atropine alone. Newly developed oxime K127 combined with atropine was the most effective in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Nevertheless, the differences of neuroprotective efficacy between K127 and obidoxime are not sufficient to replace obidoxime by K127 for the treatment of acute tabun poisonings.
- MeSH
- Chemical Warfare Agents poisoning MeSH
- Cholinesterase Inhibitors poisoning MeSH
- Rats MeSH
- Neuroprotective Agents pharmacology MeSH
- Organophosphates MeSH
- Organophosphate Poisoning * MeSH
- Oximes pharmacology MeSH
- Motor Activity drug effects MeSH
- Rats, Wistar MeSH
- Pyridinium Compounds pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Chemical Warfare Agents MeSH
- Cholinesterase Inhibitors MeSH
- K117 compound MeSH Browser
- K127 compound MeSH Browser
- Neuroprotective Agents MeSH
- Organophosphates MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- tabun MeSH Browser
The therapeutical efficacies of eleven oxime-based acetylcholinesterase reactivators were compared in an in vivo (rat model) study of treatment of intoxication caused by tabun. In this group there were some currently available oximes (obidoxime, trimedoxime and HI-6) and the rest were newly synthesized compounds. The best reactivation efficacy for acetylcholinesterase in blood (expressed as percent of reactivation) among the currently available oximes was observed after administration of trimedoxime (16%) and of the newly synthesized K127 (22432) (25%). The reactivation of butyrylcholinesterase in plasma was also studied; the best reactivators were trimedoxime, K117 (22435), and K127 (22432), with overall reactivation efficacies of approximately 30%. Partial protection of brain ChE against tabun inhibition was observed after administration of trimedoxime (acetylcholinesterase 20%; butyrylcholinesterase 30%) and obidoxime (acetylcholinesterase 12%; butyrylcholinesterase 16%).
- Keywords
- Acetylcholinesterase, butyrylcholinesterase, oximes, pretreatment, reactivators,
- Publication type
- Journal Article MeSH
