Acetylcholinesterase, comparative inhibition

Kuca, K., Jun, D., Cabal, J., Hrabinova, M., Bartosova, L., Opletalova, V. (2006). Russian VX inhibition and reactivation of acetylcholinesterase compared with VX agent. Basic Clin. Pharmacol. Toxicol. 98 389-94. 

Figure 1. Comparative inhibition (pI50) of acetylcholinesterase from susceptible (S) and two resistant (RN-N and RN-4) strains of green rice leafhopper by m-tolyl N-alkylcarbamates in which the jj-alkyl group varies from methyl to n,-butyl. Reproduced with permission from Ref. 37. Copyright 1983 Plenum Press.

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

Sandahl, J.F, Baldwin, D.H., and Jenkins, J.J. et al. (2005). Comparative thresholds for acetylcholinesterase inhibition and behavioural impairment in Coho Salmon exposed to chlorpyriphos. Environmental Toxicology and Chemistry 24, 136-145. 

Donepezil is a piperidine cholinesterase inhibitor, which reversibly and non-competitively inhibits centrally active acetylcholinesterase 34 This specificity is claimed to result in fewer peripheral side effects as compared to the other ChE inhibitors. 

Comparative Toxicokinetics. Diazinon, an anticholinesterase organophosphate, inhibits acetylcholinesterase in the central and peripheral nervous system resulting in cholinergic symptoms, in some... 

The developed biosensor was applied to the analysis of cyanobacterial bloom samples from freshwater lakes of Spain, Greece, France, Scotland and Denmark. Two samples from Scotland and one from Denmark irreversibly inhibit the acetylcholinesterase. The estimated concentrations were between 1.5 and 30nmol/g of dry weight, values extremely high when compared to the intraperitoneal 50% lethal dose of anatoxin-a(s) in mice (121 nmol/kg). 

Suresh, A., B. Sivaramakrishna, P.C. Victoriamma and K. Radhakrishnaiah. Comparative study on the inhibition of acetylcholinesterase activity in the freshwater fish Cyprinus carpio by mercury and zinc. Biochem. Int. 26 367—375, 1992. 

In a similar study using PET technology to assess the impact of cholinesterase inhibition in the cortical brain, Bohnen and colleagues enrolled 14 subjects with Alzheimer s disease who were administered donepezil for 12 weeks. Their data showed a 19 % donepezil induced acetylcholinesterase inhibition with most of the inhibition occurring at the anterior cingulate cortex [61]. The degree of acetylcholinesterase inhibition was limited in the cortex when compared with the 70-90% acetylcholinesterase inhibition normally found in peripheral red blood cells [62]. This implies that the cholinesterase in-... 

In another study, clipped rabbits were exposed to sulfur mustard, lewisite (L), thickened soman, and VX and were decontaminated between 30 s and 5 min postexposure. Eor the vesicants (sulfur mustard and L), lesion areas were compared. Decontaminating for 1 min resulted in the lesion areas being reduced 21-fold for sulfur mustard and 22-fold for L, relative to no decontamination. For the nerve agents (soman and VX), the inhibition of blood acetylcholinesterase (AChE) was used as a marker. Using a 2 min decontamination time, the dose of nerve agent required to produce 50% inhibition of AChE was increased 1.8-fold for thickened soman and 18-fold for VX (Hobson et al., 1993). 

Based on the above discussion, trifluoromethyl ketones should inhibit proteases such as chymotrypsin (32), and serine esterases, such as acetylcholinesterase (33,24)> carboxylesterases (10), JHE and other esterases with varying selectivity. In a series of some juvenoid-like trifluoromethyl ketones and compounds of the structure A, l,l,l-trifluoro-2-tetradecanone (TFT) was found to be highly active and selective against JHE (I50 lxlO 7M) as compared to a-naphthyl acetate esterase (o-NaE) or trypsin (4iJ>). 

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