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Cholinesterase ReactivatorsAcetylcholinesteraseObidoxime ChlorideOximesPralidoxime CompoundsCholinesterase InhibitorsSarinPyridinium CompoundsChemical Warfare AgentsAntidotesOrganophosphatesParaoxonButyrylcholinesteraseAcetylthiocholine
AChEInhibitorsOximesReactivationPralidoximeOxime reactivatorsCholinesterase reactivatorOrganophosphatesMechanismReversibleAntimuscarinicOrganophosphorusPotentSynthesisAffinityCompoundsContinuousCholinesterase ReactivatorsOximeAcetylcholineAldoxime ReactivatorsInhibition of acetylcholinesteraseReactivationInhibitPralidoximeMuscarinic antagonistOrganophosphateVitroCrystallographySerineComplexMedications
AChE19
  • Inhibition of the enzyme acetylcholinesterase (AChE) is the main mechanism both of therapeutic action of drugs for the treatme. (nel.edu)
  • Afterwards, an enzyme known as acetylcholinesterase (AChE) arrives to remove the ACh molecule. (llnl.gov)
  • Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. (simulations-plus.com)
  • Present study evaluates reactivation potency of two newly developed oximes, K456 and K733, against paraoxon (POX)-inhibited human-RBC-AChE and human-plasma-BChE in comparison to reported reactivator, pralidoxime (2-PAM). (simulations-plus.com)
  • Both in vitro and in silico studies conclude that K456 and K733 are unlikely to be used as reactivators of paraoxon-inhibited AChE or BChE. (simulations-plus.com)
  • The toxicity of OPNAs stems from covalent inhibition of the essential enzyme acetylcholinesterase (AChE), which reactivators relieve via a chemical reaction with the inactivated enzyme. (ox.ac.uk)
  • Our results show that new OPNA reactivators can be discovered rationally by exploiting detailed knowledge of the reactivation mechanism of OPNA-inhibited AChE. (ox.ac.uk)
  • Prophylactic i.v. injection of IIG1 (1 mg/kg) prevented systemic toxicity in cyclosarin (~2LD50)-poisoned guinea pigs, preserved brain acetylcholinesterase (AChE) activity, and protected erythrocyte AChE activity partially. (inra.fr)
  • OP inhibit acetylcholinesterase (AChE) and therefore standard treatment of respective poisoning includes AChE reactivators (oximes) in combination with antimuscarinic agents. (inra.fr)
  • Organophosphorus compounds are known to inhibit the enzyme acetylcholinesterase (AChE). (stackexchange.com)
  • Acute OP toxicity is primarily due to inhibition of acetylcholinesterase (AChE), an enzyme in the central and peripheral nervous system. (inrae.fr)
  • OP inhibition of AChE can be reversed using oxime reactivators but many show poor CNS penetration, indicating a need for new clinically viable reactivators. (inrae.fr)
  • In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. (tno.nl)
  • The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by organophosphates (OPs) as nerve agents and pesticides compromises normal cholinergic nerve signal transduction in the peripheral and central nervous systems (CNS) leading to cholinergic crisis. (irb.hr)
  • Eight trans, anti- and trans, syn-isomers of oximes were tested as reactivators of nerve agent-inhibited AChE and BChE. (irb.hr)
  • We describe in this article development and properties of new human acetylcholinesterase (AChE) crystals of space group P3 1 and a new unit cell, amenable for room-temperature X-ray diffraction studies. (rcsb.org)
  • Treatment against acute OP toxicity includes oximes which reactivate phosphorylated acetylcholinesterase (AChE) restoring enzymatic activity. (msstate.edu)
  • Nerve agents are compounds that have the capacity to inactivate the enzyme acetylcholinesterase (AChE). (medscape.com)
  • Nerve agents inhibit the enzyme acetylcholinesterase (AChE), which hydrolyzes the neurotransmitter acetylcholine (ACh) once ACh has finished activating receptors in neurons, muscles, and glands. (msdmanuals.com)
Inhibitors4
  • In vitro effects of acetylcholinesterase inhibitors and reactivators on Complex I of electron transport chain. (nel.edu)
  • Physostigmine's poor tolerability led to it being abandoned in favor of later acetylcholinesterase inhibitors, three of which are currently in use: donepezil, galantamine, and rivastigmine. (wikipedia.org)
  • Many of the acetylcholinesterase inhibitors listed above act as butyrylcholinesterase inhibitors. (arabsciencepedia.org)
  • We discover suitable inhibitor scaffolds by using an activity-independent competition assay to study non-covalent interactions with OPNA-AChEs and transform these inhibitors into broad-spectrum reactivators. (ox.ac.uk)
Oximes3
  • The goal of study was the determination of the ionization constants for the oximes - cholinesterases reactivators in aqueous solutions at different temperatures. (bmc-rm.org)
  • Spectrophotometric and electrochemical study of protolytic equilibria of some oximes-acetylcholinesterase reactivators. (bmc-rm.org)
  • These data indicate that the novel pyridinium oximes are equally efficacious reactivators in adult and juvenile rats of both sexes and enhance survivability against lethal-level OP toxicity as compared to 2-PAM in adult female rats. (msstate.edu)
Reactivation3
Pralidoxime3
  • Pralidoxime is a cholinesterase reactivator used to treat organophosphate poisoning. (drugbank.com)
  • If given within 24 hours,after organophosphate exposure, pralidoxime reactivates the enzyme cholinesterase by cleaving the phosphate-ester bond formed between the organophosphate and acetylcholinesterase. (drugbank.com)
  • Although drugs like obidoxime or pralidoxime have been used with considerable success, there is a need for new substances capable of reactivating acetylcholinesterase with a broader scope and increased efficacy. (irb.hr)
Oxime reactivators1
  • Successful solution of the new room temperature 3.2 Å resolution structure of BW284c51*hAChE complex from large P3 1 crystals enables us to proceed with studying room temperature structures of lower affinity complexes, such as oxime reactivators bound to hAChE, where temperature-related conformational diversity could be expected in both oxime and hAChE, which could lead to better informed structure-based design under conditions approaching physiological temperature. (rcsb.org)
Cholinesterase reactivator1
  • To exclude genetic or nutritional causes for the low enzyme activity, a cholinesterase reactivator, prallidoxime (4 pg per 500 ml blood), was introduced to reactivate the cholinesterase in the two samples and in the controls. (dlawer.info)
Organophosphates1
Mechanism2
Reversible1
  • It is a reversible inhibitor of acetylcholinesterase, the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft of the neuromuscular junction. (wikipedia.org)
Antimuscarinic1
  • The treatment comprises an antimuscarinic drug and an oxime reactivator of the inhibited enzyme. (irb.hr)
Organophosphorus1
  • Reactivators are vital for the treatment of organophosphorus nerve agent (OPNA) intoxication but new alternatives are needed due to their limited clinical applicability. (ox.ac.uk)
Potent1
  • HLo 7 was the most potent reactivator followed by HI 6 and obidoxime while 2-PAM and MMB-4 were rather weak reactivators. (inra.fr)
Synthesis2
Affinity1
  • Possible screening candidates must fulfill two fundamental requirements: They must (i) show an affinity to acetylcholinesterase well balanced between sufficient binding and competitive inhibition and (ii) facilitate the nucleophilic cleavage of the phosphorylated catalytic serine residue. (irb.hr)
Compounds1
Continuous1
  • Acetylcholinesterase inhibition causes acetylcholine to accumulate in synapses, producing continuous stimulation of cholinergic fibers throughout the nervous systems. (drugbank.com)
Cholinesterase Reactivators1
Oxime5
Acetylcholine3
  • The duration of actionof acetylcholine is limited, due to the inactivation by acetylcholinesterases. (pharmapdf.com)
  • Reactivated acetylcholinesterase hydrolyzes excess acetylcholine resulting from organophosphorus poisoning to help restore impaired cholinergic neural function. (empr.com)
  • We here report observations on the distribution of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) in the striatum of the adult human, the rhesus monkey, and the cat. (lookformedical.com)
Aldoxime Reactivators2
  • 10. Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon. (nih.gov)
  • We thus show that rational design based on structural studies permits the refinement of new-generation pyridine aldoxime reactivators that may be more effective in the treatment of nerve agent intoxication. (inrae.fr)
Inhibition of acetylcholinesterase1
Reactivation7
  • Bharate SB, Chao CK, Thompson CM. Comparison of the reactivation rates of acetylcholinesterase modified by structurally different organophosphates using novel pyridinium oximes. (nih.gov)
  • 1. Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker: preparation and reactivation of tabun- and paraoxon-inhibited acetylcholinesterase. (nih.gov)
  • 2. Novel series of bispyridinium compounds bearing a (Z)-but-2-ene linker--synthesis and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. (nih.gov)
  • 5. Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase. (nih.gov)
  • 7. In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075--to reactivate tabun-inhibited human brain cholinesterases. (nih.gov)
  • 11. In vitro reactivation of tabun-inhibited acetylcholinesterase using new oximes--K027, K005, K033 and K048. (nih.gov)
  • These results offer insights into the reactivation mechanism of HI-6 and design of better reactivators. (inra.fr)
Inhibit1
  • We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT4 receptor, which displays promising activities in vivo. (inrae.fr)
Pralidoxime2
  • Pralidoxime reactivates acetylcholinesterase which has been inactivated by phosphorylation due to an organophosphorus nerve agent or insecticide. (empr.com)
  • DuoDote, a combination of atropine, a cholinergic muscarinic antagonist, and pralidoxime chloride, a cholinesterase reactivator, is indicated for the treatment of poisoning by organophosphorus nerve agents as well as organophosphorus insecticides in adults and pediatric patients weighing more than 41 kg (90 pounds). (nih.gov)
Muscarinic antagonist1
  • Cholinergic muscarinic antagonist + cholinesterase reactivator. (empr.com)
Organophosphate1
  • 9. Monooxime Bispyridinium Reactivators Bearing Xylene Linker Synthesis and In Vitro Evaluation on Model of Organophosphate-Inhibited Acetylcholinesterase. (nih.gov)
Vitro1
Crystallography1
  • Gerlits O, Ho KY, Cheng X, Blumenthal D, Taylor P, Kovalevsky A, Radić Z. A new crystal form of human acetylcholinesterase for exploratory room-temperature crystallography studies. (nih.gov)
Serine2
Complex1
Medications1