Acetylcholinesterase, inhibition reversible

Inhibits serine proteases such as trypsin and chymotrypsin. Also inhibits cysteine proteases (reversible by reduced thiols) and mammalian acetylcholinesterase Inhibits ATPase, alkaline phosphatase and tyrosine phosphatase Reagent for maintaining -SH groups in the reduced state. Effective for reducing protein disulfide bonds prior to SDS-PAGE... 

Wilson, I.B. Acetylcholinesterase. XI. Reversibility of tetraethyl pyrophosphate inhibition. J. Biol. Chem. 

A third approach to protection against excessive acetylcholinesterase inhibition is pretreatment with reversible enzyme inhibitors to prevent binding of the irreversible organophosphate inhibitor. This prophylaxis can be achieved with pyridostigmine but is reserved for situations in which possibly lethal poisoning is anticipated, eg, chemical warfare (see Chapter 7). Simultaneous use of atropine is required to control muscarinic excess. 

Tike the OP insecticides, the mode of action of the carbamates is acetylcholinesterase inhibition with the important difference that the inhibition is more rapidly reversed than with OP compounds. 

Although OPPs and carbamates exhibit very similar modes of action in various animal species, i.e, acetylcholinesterase inhibition in the CNS with resulting paralysis—there is an important difference between the two classes of pesticides. Carbamates do not require metabolic conversion prior to exhibiting their toxicity. Furthermore the enzyme activity may at times be rapidly regenerated by reversal of inhibition. The kinetics of the inhibition (carbamoylation) reaction have been well studied in it electrophilic carbamoyl moieties form covalent bonds with enzyme esteratic sites. This is followed by carbamate transfer of an acidic group to the site to yield the acetylated enzyme complex (ref. 176). 

Reversible and competitive acetylcholinesterase inhibition leading to an increased concentration of acetylcholine at cholinergic synapses modulates nicotinic acetylcholine receptor may increase glutamate and serotonin levels APOE, APP... 

Lennox, W.J., Harris, L.W., Talbot, B.G, and Anderson, D.R., Relationship between reversible acetylcholinesterase inhibition against soman lethality, Life Sci, 37,793-798,1985. 

Wilson IB. Acetylcholinesterase, XI Reversibility of tetra ethylpyrophosphate inhibition. J Biol Chem. 1951 190 111-117. 

Carbamate poisoning produces reversible acetylcholinesterase inhibition, and spontaneous recovery of enzyme activity may occur within several hours, making these tests less usehl. 

Lennox WJ, Harris LW, Talbot BG, Anderson DR (1985) Relationship between reversible acetylcholinesterase inhibition and efficacy against soman lethality. Life Sci 37 793-798. (Cited in Somani et al. 1992.)... 

Jatrorrhizine (69) and palmatine (78) are active against Plasmodium falciparum. Jatrorrhizine inhibits butyrylchol-inesterase (Wink, 1993). Palmatine inhibits reverse transcriptase, aldose reductase, and acetylcholinesterase (Wink, 1993). 

Recently reported effects of commint include acetylcholinesterase inhibition (linarin) and reversible antifertility. 

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... 

ACh is metabolised extraneuronally by the enzyme acetylcholinesterase, to reform precursor choline and acetate. Blocking its activity with various anticholinesterases has been widely investigated and some improvement in memory noted. Such studies have invariably used reversible inhibition because of the toxicity associated with long-term irreversible inhibition of the enzyme. Physostigmine was the pilot drug. It is known to improve memory in animals and some small effects have been seen in humans (reduces number of mistakes in word-recall tests rather than number of words recalled), but it really needs to be given intravenously and has a very short half-life (30 min). 

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. 

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