Inhibition of acetylcholinesterase AChE

Conventional nerve agents, such as sarin and soman, are OP compounds of pentavalent phosphorus that are well known as threats in the context of warfare and terrorism (Sidell and Borak, 1992). These substances produce acute cholinergic toxicity and death via inhibition of acetylcholinesterase (AChE) in the central and peripheral nervous systems (Marrs et al, 1996). 

Tacrine has numerous mechanisms of action. The putative principle mechanism of action of tacrine for Alzheimer s disease is reversible inhibition of acetylcholinesterase (AChE), which thereby slows the breakdown of the chemical messenger acetylcholine (ACh) in the brain. In addition, tacrine blocks the sodium and potassium channels. 

Organophosphorus compounds (OPC) cause two major toxic effects. The first is the well-known acute toxicity initiated by inhibition of acetylcholinesterase (AChE) with subsequent accumulation of acetylcholine at nerve endings. The second effect is organophosphate-induced delayed polyneuropathy (OPIDP) (ataxia and paralysis appearing 2-3 weeks after exposure) associated with inhibi-... 

A new metabolite (5)-einnamoylphosphoramide (73) from Streptomyces sp. JP90, has been synthesized by Zezschwitz et al. The absolute configuration at the phosphorus atom was determined by synthesis of both enantiomers of (73). The unusual derivatives represented the first bacterial organophosphoramides and showed biological activity against arthropods and a weak inhibition of acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) in preliminary in vim tests. 

Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110 5959-5967 Crane AL, Browner RW, Knaak JB, Bonner MR, Fenske RA, Farahat FM, Anger WK, Lein PJ, Olson JR (2011) Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in human blood following in vitro and in vivo exposure to chlorpyrifos. Abstract No. 1243, 49th Annual Meeting and ToxExpo, Salt Lake City, Utah, March 7-11. 

The OPs exert their main toxicological effects by non-reversible phosphorylation of esterases in the central nervous system, whereas the acute toxic effects are related to inhibition of acetylcholinesterase (AChE) (Sogorb and Vilanova 2002). AChE is a very efficient enzyme, since one unique molecule hydrolyses approximately 5,000 acetylcholine (ACh) molecules per second (Schofield and Dinovo 2010). ACh is a chemical mediator, needed for transmission of nerve impulses, present in mammals and insects (Santos et al. 2007). 

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