Compounds cholinesterase reactivators. Medical search. Frequent questions

The role and proper dose of pralidoxime in the treatment of Organophosphorus (OP) compounds poisoning is an unresolved issue .This study was designed to compare the regimen recommended by the World Health Organization (WHO) with the commonly used standard regimen of pralidoxime. (ac.ir)
Organophosphorus (OP) compounds are widely used as insecticides and pesticides (1). (ac.ir)
Jamal GA. Neurological syndromes of organophosphorus compounds. (cdc.gov)
Organophosphorus compounds are known to inhibit the enzyme acetylcholinesterase (AChE). (stackexchange.com)
Significance Statement Paraoxon (POX) is an organophosphorus (OP) compound and a powerful prototype and substitute for OP chemical warfare agents (CWAs) such as sarin, VX etc. (inrae.fr)
The designation "nerve gas" or "nerve agent" is used for organophosphorus compounds that inhibit tissue cholinesterase. (who.int)
More than 95% of this activity is inhibited in assays where substrate has been added to a preincubated mixture of tissue with the non-neuropathic organophosphorus compound (OP) paraoxon (O,O'-diethyl p-nitrophenyl phosphate): residual activity includes soluble neuropathy target esterase (S-NTE) which, by definition, is considered resistant to long-term progressive (covalent) inhibition by paraoxon. (inrae.fr)

OP pesticides inhibit carboxylic esterase enzymes including acetyl cholinesterase (AChE) and plasma cholinesterase (PChE) through binding to the esteratic site on the AChE molecule, phosphorylating the enzyme. (ac.ir)
Most of the compounds were estimated to be able to cross the blood-brain barrier (BBB) by passive transport and were nontoxic to human neuronal, kidney and liver cells in concentrations in which they inhibit cholinesterases. (inra.fr)
Organophosphate Poisoning and Carbamate Poisoning Organophosphates and carbamates are common insecticide ingredients that inhibit cholinesterase activity, causing acute muscarinic manifestations (eg, salivation, lacrimation, urination, diarrhea. (msdmanuals.com)

Cholinesterase reactivators: oxime compounds are used, eg. (pediatriconcall.com)
The treatment comprises an antimuscarinic drug and an oxime reactivator of the inhibited enzyme. (irb.hr)
A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. (bvsalud.org)
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)

Eight trans, anti- and trans, syn-isomers of oximes were tested as reactivators of nerve agent-inhibited AChE and BChE. (irb.hr)
Based on modarate binding affinity of both AChE and BChE for all selected oximes, and in silico evaluated ADME properties regarding lipo-philicity and CNS activity, these compounds present new class of oximes with potential for the further development of CNS-active therapeutics in OP poisoning. (irb.hr)
Considering that acetylcholinesterase (AChE) inhibition is the most important mode of action expected of a potential drug used for the treatment of symptoms of Alzheimer's disease (AD), our previous pilot study of 4-aminoquinolines as potential human cholinesterase inhibitors was extended to twenty-two new structurally distinct 4-aminoquinolines bearing an adamantane moiety. (inra.fr)
Inhibition studies revealed that all of the compounds were very potent inhibitors of AChE and butyrylcholinesterase (BChE), with inhibition constants (K(i)) ranging between 0.075 and 25 microM. (inra.fr)
the most selective for BChE was compound 14, which displayed a 10 times higher preference, while compound 19 was a 5.8 times more potent inhibitor of AChE. (inra.fr)

They are irreversible competitive inhibitors of enzyme Acetyl Cholinesterase. (pediatriconcall.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)
Organophosphates form an initially reversible bond with the enzyme cholinesterase. (medscape.com)

Valuable material was used up in the screening process, and it was only as a last resort that the two remaining specimens were tested for cholinesterase inhibition. (dlawer.info)
Following intraperitoneal administration of fensulfothion (0.9 mg/kg) to rats, inhibition of cholinesterase was maximal within one hour. (inchem.org)
Among them, two compounds stand out: compound 5 as the most potent inhibitor of both cholinesterases with a K(i) constant in low nano molar range and the potential to cross the BBB, and compound 8, which met all our requirements, including high cholinesterase inhibition, good oral bioavailability, and antioxidative effect. (inra.fr)

Screening for nitrogen/phosphorus compounds was done by gas chromatography and gas chromatography/mass spectrometry. (dlawer.info)
Gas chromatography of the test blood samples revealed only one significant peak, indicating a nitrogen/phosphorus compound. (dlawer.info)

Pralidoxime is to reactivate cholinesterase (mainly outside of the central nervous system) which has been inactivated by phosphorylation due to an organophosphate pesticide or related compound. (drugbank.com)
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)

Insecticides: organic phosphorus compounds and carbamates. (cdc.gov)

Pralidoxime also slows the process of 'aging' of phosphorylated cholinesterase to a nonreactivatable form, and detoxifies certain organophosphates by direct chemical reaction. (drugbank.com)
Prallidoxime will also remove organophosphates attached to the activity site of the cholinesterase causing an increase in enzyme activity. (dlawer.info)

In this paper, we extended our study on 4-aminoquinolines as human cholinesterase inhibitors on twenty-six new 4-aminoquinolines containing an n-octylamino spacer on C(4) and different substituents on the terminal amino group. (inra.fr)

Effect on enzymes and other biochemical parameters Fensulfothion, like other organophosphorothionate esters, is a weak cholinesterase inhibitor which, after being converted to the corresponding phosphate ester of fensulfothion is from 500 to 2 000 times more active in inhibiting cholinesterase. (inchem.org)

These compounds cause 80% of the reported toxic exposures to insecticides. (medscape.com)
however, their widespread use began in Germany in the 1920s, when these compounds were first synthesized as insecticides and chemical warfare agents. (medscape.com)

Pralidoxime chloride is a cholinesterase reactivator. (nih.gov)
Regardless of whether or not animal studies suggest that the organophosphate poison to which a particular patient has been exposed is amenable to treatment with pralidoxime chloride, the use of pralidoxime chloride should, nevertheless, be considered in any life-threatening situation resulting from poisoning by these compounds, since the limited and arbitrary conditions of pharmacologic screening do not always accurately reflect the usefulness of pralidoxime chloride in the clinical situation. (nih.gov)
In one study of healthy adult volunteers and patients self-poisoned with organophosphate compounds, a single intramuscular injection of 1000 mg of pralidoxime chloride resulted in mean peak plasma levels of 7.5 ± 1.7 µg/mL and 9.9 ± 2.4 µg/mL, respectively. (nih.gov)

1 Rat brain cholinesterase, molar concentration inducing 50% inhibitions. (inchem.org)

Atropine antagonizes the muscarinic effects of OP compounds. (ac.ir)

Pralidoxime is a cholinesterase reactivator used to treat organophosphate poisoning. (drugbank.com)
The organophosphate-cholinesterase bond can spontaneously degrade, reactivating the enzyme, or can undergo a process called aging. (medscape.com)

Selective affinity relies on a compound binding with higher affinity to the alpha2/alpha3 compared with alpha1 subtypes, but to date no such compounds have been described. (hhs.gov)

The onset and severity of symptoms, whether acute or chronic, depends upon the specific chemical, the route of exposure (skin, lungs, or GI tract), the dose, and the individuals ability to degrade the compound, which the PON1 enzyme level will affect. (wikipedia.org)

In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. (bvsalud.org)
Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). (bvsalud.org)
They are also called Novichok agents, and representative compounds are A-230, A-232, and A-234, which are liquids that are even more persistent than V-series agents and are just as potent. (msdmanuals.com)

Interest in the effects of these compounds on humans has increased in recent years due to their potential use as weapons of mass destruction. (medscape.com)

Generally, newly synthesised compounds were weak reductants compared to standard antioxidants, but all possessed a certain amount of antioxidant activity compared to tacrine. (inra.fr)

The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 µM), leading to its selection for further investigation. (bvsalud.org)
Compounds which restore enzymatic activity by removing an inhibitory group bound to the reactive site of the enzyme. (bvsalud.org)
Cholinesterase activity was assessed in two blood samples by measuring the changes in absorbence at 405 nm (EPOS 5060 analyser) resulting when the chromogen 5,5'?dithiobis(4-nitrobenzoic acid) reacts with the thiocholine iodide produced by the action of the enzyme on a highly diluted sample of acetylthiocholine iodide. (dlawer.info)
To ensure that high ambient temperatures had not reduced the cholinesterase activity, a standard solution of pure enzyme was kept at 25oC for five days. (dlawer.info)
In control samples a large concentration of 2 - hydmxyethylbenzthiazol (200 mg/ml) had no detectable effect on cholinesterase activity either immediately or after five days' incubation at room temperature. (dlawer.info)
There was only a very small and not significant decrease in cholinesterase activity. (dlawer.info)
As with several other compounds of a similar structural nature, cholinesterase activity in females is more sensitive to in vivo anti-cholinesterase activity. (inchem.org)
The tested compounds displayed modest but generally higher antioxidant activity than the structurally similar AD drug tacrine. (inra.fr)

Cholinesterases rapidly hydrolyze the neurotransmitter acetylcholine into inactive fragments. (medscape.com)

Binding to the esteratic site on the enzyme is stable and depending on the compound involved, it can last for hours or weeks (1). (ac.ir)
The status of these and other BZ site compounds with claimed, but often not explicitly stated, GABA(A) subtype selectivity (such as ELB-139 and ocinaplon) will be reviewed in relation to their development as non-sedating anxiolytics for the treatment of generalised anxiety disorder. (hhs.gov)

In many developing countries including India, OP compounds are easily available and are common cause of both intentional and accidental poisonings (2-5). (ac.ir)
Being predominantly an agricultural country, OP compounds are used abundantly for farming in India. (ac.ir)

Evaluation of druglikeness singled out fourteen compounds with possible oral route of administration. (inra.fr)

Cholinesterase is found in two forms: an RBC form, which is known as true cholinesterase, and a plasma form, which is known as pseudocholinesterase. (medscape.com)

OPLETAL, L.: Modernization and extension of the doctoral study field of Pharmacognosy and Toxicology of Natural Compounds within the Pharmacy study program. (cuni.cz)

However, despite their proven clinical anxiolytic efficacy, such compounds possess a relatively narrow window between doses that produce anxiolysis and those that cause sedation, and are also associated with physical dependence and a potential for abuse. (hhs.gov)

Compound 19 showed the highest reducing power, comparable to those of standard antioxidants. (inra.fr)

Alkyl-bridged quaternary amines (e.g. bis-pyridinium aldoximes) did not show metabolic N-dealkylation or alkyl transfer to another compound. (otka-palyazat.hu)

Self-poisoning with OP compounds is a serious health problem especially in agricultural areas of developing countries (2). (ac.ir)

Diseases1

Chemicals and Drugs42

Technology, Industry, Agriculture1

Organophosphorus7

Inhibit3

Oxime4

AChE5

Acetyl Cholinesterase1

Enzyme cholinesterase2

Inhibition3

Chromatography2

Reactivate2

Phosphorus compounds1

Organophosphates2

Inhibitors1

Inhibitor1

Insecticides2

Pralidoxime chloride3

Molar1

Muscarinic1

Organophosphate2

Selective1

Degrade1

Potent3

Humans1

Weak1

Activity8

Acetylcholine1

Site2

India2

Administration1

Plasma1

Study1

Potential1

Standard1

Show1

Health1