The value of novel oximes for treatment of poisoning by organophosphorus compounds

Cholinesterase Inhibitors

“…This and the effects of daily life exposure to anti ChEs in agriculture and industry led to the development of detection methods and therapeutic agents to prevent the lethal effects of antiChEs (Periasamy et al, 2009;Masson, 2011;Worek and Thiermann, 2013).…”

“…Current medical intervention in the case of acute exposure to antiChE agents includes the use of the muscarinic receptor antagonist atropine to block over stimulation, and oximes to reactivate OPmodified cho linesterases (Worek and Thiermann, 2013). However, these conventional treatments have limited effective ness and may involve serious short and longterm side effects (Worek and Thiermann, 2013).…”

“…However, these conventional treatments have limited effective ness and may involve serious short and longterm side effects (Worek and Thiermann, 2013). In fact, the rou tine treatments, while successfully decreasing antiChE induced lethality, rarely alleviate postexposure toxicity and result in significant performance deficits and even permanent brain damage (Masson, 2011).…”

“…Indeed, the 1:1 stoichiometry necessary for antiChE bioscavenging by ChEs, stemming from the virtual irreversibility of the interaction of the enzymes with the inhibitors, is one of the major limitations of this approach. Coadministration of oximes to enhance regeneration of the bioscavengers after OP exposure is only partially effective (and it is not effective at all against some nerve agents, such as tabun and soman) and the chemistry involved in the process results in highly reactive and toxic phosphylox imes (Worek and Thiermann, 2013).…”

Synthesis and in vitro kinetic evaluation of N-thiazolylacetamido monoquaternary pyridinium oximes as reactivators of sarin, O-ethylsarin and VX inhibited human acetylcholinesterase (hAChE)

“…[28][29][30] In the development of versatile and effective medical countermeasures against acute OP poisoning, extensive variations in the structural features of oxime reactivators are needed for further refinement to shape-up a broad spectrum antidote. 31,32 2. Synthesis and chemistry of N-thiazolylacetamido pyridinium oximes…”