https://doi.org/10.15255/KUI.2003.008
Published: Kem. Ind. 53 (9) (2004) 401–409
Paper reference number: KUI-08/2003
Paper type: Review
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Imidazolium and Quinuclidinium Compounds – Potential Antidotes in Organophosphorus Poisoning

I. Primožič and S. Tomić Pisarović

Abstract

Organophosphorus (OP) compounds used as pesticides and nerve agents inhibit the enzyme acetylcholinesterase (AChE) essentially irreversibly. Bisquaternary pirydinium oximes are well known antidotes against OP poisoning but no fully satisfactory regimen has been found yet. In this survey, syntheses and antidotal properties of two classes of compounds – imidazolium and quinuclidinium – with possible multiple actions in cholinergic system are discussed. N-alkyl imidazolium aldoxime derivatives are compounds with the usually high affinity for the catalytic site of the enzyme. The primary antidotal effect of imidazolium oximes is reactivation of phosphorylated AChE. Antidotal efficacy of 3-substituted quinuclidinium derivatives is the result of their interaction with AChE and/or other receptors in the cholinergic system (e.g. suppression of presynaptic synthesis of acetylcholine). Several bisquaternary imidazolium- pyridinium, quinuclidinium-pyridinium and imidazolium-quinuclidinium oximes have been synthesized in order to investigate the properties of compounds containing both moieties in the same molecule. Some of these derivatives proved to be good antidotes against OP poisoning. Compounds were discussed as reversible inhibitors, acylating agents, protectors against phosphorylation, and reactivators of AChE phosphorylated by some OP compounds.

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Keywords

acetylcholinesterase, organophosphorus inhibitors, imidazolium and quinuclidinium compounds, protection of enzyme, reactivation by oximes