Recently, several bis-pyridiniumaldoximes linked by a variable-length alkylene chain were rationally designed in our laboratories as cholinesterase reactivators. Extensive in vitro tests of these oximes with acetylcholinesterase inhibited by two different organophosphate agents, echothiophate and diisopropylfluorophosphate, revealed one compound with particularly good reactivation kinetics and ...

Basic mechanism of action of organophosphates (OP)/nerve agents is based on acetylcholinesterase (AChE) inhibition and subsequent accumulation of neuromediator acetylcholine at the cholinergic synapses, either peripheral or central, causing cholinergic hyperstimulation and development of symptoms of poisoning, followed by metabolic dysbalance and, without eff ective prophylaxis/treatment leadin...

We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular ...

A methodology combining molecular structure represented by fragments, and artificial neural network (ANN) was applied for the prediction of a new acetylcholinesterase (AChE; EC 3.1.1.7) reactivator. We searched for a new structure of the AChE reactivator with the capability of reactivating AChE inhibited by almost all actual nerve agents. For this purpose, we have tested in vitro seventeen pote...

A simple and reliable HPLC method for determination of rat plasma levels of clinically used acetylcholinesterase (AChE) reactivators (HI-6 and obidoxime) is presented in our study. Separation was carried out by HPLC using an octadecyl silica stationary phase and a mobile phase consisting of 24% acetonitrile and containing 5 mM sodium octanesulfonate and 5 mM tetramethylammonium chloride (pH 2.3...

This paper describes an in vitro study of three potential acetylcholinesterase (AChE; EC 3.1.1.7) reactivators derived from a monoquaternary reactivator pralidoxime. Compounds used were pyridinium-2-aldoxime-4-carbamoyl-N-methyl iodide (TO231), pyridinium-2-aldoxime-4-ethoxycarbonyl-N-methyl iodide (TO237), and pyridinium-2-aldoxime-5-ethoxycarbonyl-N-methyl iodide (TO238). Pralidoxime and obid...

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 per...

We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylc...

Acetylcholinesterase has important role in synaptic cleft. It breaks down the acetylcholineat cholinergic synapsesand terminates the cholinergic effects. Some chemical agents like organophosphorus compounds (OPCs) including nerve agents and pesticides react with acetylcholinesteraseirreversibly. They inhibit normal biological enzyme action and result in accumulation of acetylcholineand show tox...