2-Hydroxyiminomethyl-<i>N</i>-Methylpyridinium Methanesulphonate (P2S), An Antidote to Organophosphorus Poisoning. Its Preparation, Estimation and Stability

Creasey, N. H.; Green, A. L.

doi:10.1111/j.2042-7158.1959.tb12586.x

Cited by 66 publications

(10 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Creasey & Green (44) and Way and co-workers (45,46) have independently employed this enhanced molar absorptivity of 2-PAM in alkaline solution to measure the 2-PAM content in various biologic tissues. The ultraviolet procedure has proved to be a more specific method for measuring 2-PAM than the conventional colorimetric bound oxime method, and a far more convenient one in application as well.…”

mentioning

confidence: 97%

The Metabolism of the Alkylphosphate Antagonists and its Pharmacologic Implications

Way¹,

Way²

1968

Annu. Rev. Pharmacol.

View full text Add to dashboard Cite

Studies on the metabolic disposition of chemical compounds have so accelerated in the past few years that if a general review of the subject for the last year were attempted, it would be possible to give no more than a sketchy summary of the voluminous literature in the space allocated. More comprehensive reviews on the general topic of drug metabolism are available as monographs (1-3). The present review, like many previous ones appear ing in this series on drug metabolism (4-6), is restricted to selected topics, and is primarily concerned with a descriptive and interpretive appraisal of the status of the alkylphosphate antagonists, also known as the cholinesterase reactivators. These compounds are of interest because of their ability to antagonize the toxic effects of the organophosphorous cholinesterase inhibi tors that are used as insecticides and war gases.All compounds in the alkylphosphate antagonist series are nucleophilic agents and are mainly oximes. Although the organic oximes have been em ployed by chemists for a number of years, very little is really known con cerning the biotransformation of this functional group. Yamafugi and co workers (7-9) have investigated the metabolism of organic oximes in plants, silkworms, and other animals. Mahadevan ( 10) has reported on the metabo lism of 3-indoleacetaldoxime from various plants and fungi. However, the impetus to investigate the biotransformation of oximes can be attributed primarily to the work of Wilson and co-workers (11)(12)(13)(14) and Childs et al. (15), who have made important contributions in the development of the cholinesterase reactivation properties of these compounds.Initially, it was believed that the alkylphosphates were such potent inhibitors of acetylcholinesterase as well as other esterases, that they pro duced an "irreversible" inhibition of this enzyme. Subsequent work, howl The survey of literature pertaining to this review was completed in May, 1967.

show abstract

mentioning

confidence: 97%

The Metabolism of the Alkylphosphate Antagonists and its Pharmacologic Implications

Way¹,

Way²

1968

Annu. Rev. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…The injections were given at 20 min intervals into the upper outer aspect of the thigh. Blood samples for assay of P2S content (Creasey and Green, 1959) were obtained by venepuncture from the median cubital vein. Subjects receiving two and three P2S injections donated blood samples immediately before each injection and at 10, 20, 30, and 60 min after the final injection.…”

Section: Methodsmentioning

confidence: 99%

Plasma concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration.

Holland¹,

Parkes²

1976

Occupational and Environmental Medicine

View full text Add to dashboard Cite

concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration. The use of the oxime P2S as intravenous therapy for organophosphorus anticholinesterase poisoning is well known. In emergency situations this route of administration may prove impractical due to severe symptoms of anticholinesterase poisoning and therefore the intramuscular route is to be preferred. The absolute intramuscular dose of P2S per man, recommended as necessary for adequate therapy of anticholinesterase poisoning, is 500 mg. In practical situations this dose may have to be repeated at intervals resulting in overdosage, and therefore the clinical side-effects which this regimen might have on normal subjects has been determined. It has also been suggested that where organophosphorus anticholinesterase compounds are handled continuously for many months in the year, for example, in crop spraying and in industry, P2S might be taken prophylactically. The effects that such a regimen might have when combined with therapeutic procedures in human subjects have therefore been evaluated. The absolute intramuscular P2S dose of 500 mg when repeated three times at 20-minute intervals in normal subjects produces no clinical sideeffects. However, when this procedure is superimposedupon an oral P2S prophylactic regimen, up to 60% of the individuals complain of visual side-effects which may prove a hazard in cases of mild anticholinesterase poisoning. It is suggested that these visual side-effects are caused by an accumulation of P2S in the eye during prolonged oral administration.

show abstract

“…2‐PAM is rapidly distributed and exhibits terminal elimination half‐lives (t 1/2β ) of 70–80 min in healthy man (i.v …”

Section: Introductionmentioning

confidence: 99%

“…Numerous early publications are focused on the characterization of 2‐PAM in terms of in vitro stability and pharmacokinetics in diverse species including man, cat, dog, rabbit, and guinea pig . These studies were conducted with related variants of spectroscopic procedures to quantify specimens of whole blood, plasma, urine, aqueous humour, tissue, and faeces.…”

Section: Introductionmentioning

confidence: 99%

Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2‐PAM)

John¹,

Blum

2011

Drug Testing and Analysis

View full text Add to dashboard Cite

Pralidoxime (2-PAM) belongs to the class of monopyridinium oximes with reactivating potency on cholinesterases inhibited by phosphylating organophosphorus compounds (OPC), for example, pesticides and nerve agents. 2-PAM represents an established antidote for the therapy of anticholinesterase poisoning since the late 1950s. Quite high therapeutic concentrations in human plasma (about 13 µg/ml) lead to concentrations in urine being about 100 times higher allowing the use of less sensitive analytical techniques that were used especially in the early years after 2-PAM was introduced. In this time (mid-1950s until the end of the 1970s) 2-PAM was most often analyzed by either paper chromatography or simple UV spectroscopic techniques omitting any sample separation step. These methods were displaced completely after the establishment of column liquid chromatography in the early 1980s. Since then, diverse techniques including cation exchange, size-exclusion, reversed-phase, and ligand-exchange chromatography have been introduced. Today, the most popular method for 2-PAM quantification is ion pair chromatography often combined with UV detection representing more than 50% of all column chromatographic procedures published. Furthermore, electrophoretic approaches by paper and capillary zone electrophoresis have been successfully used but are seldom applied. This review provides a commentary and exhaustive summary of analytical techniques applied to detect 2-PAM in pharmaceutical formulations and biological samples to characterize stability and pharmacokinetics as well as decomposition and biotransformation products. Separation techniques as well as diverse detectors are discussed in appropriate detail allowing comparison of individual preferences and limitations. In addition, novel data on mass spectrometric fragmentation of 2-PAM are provided.

show abstract

2-Hydroxyiminomethyl-N-Methylpyridinium Methanesulphonate (P2S), An Antidote to Organophosphorus Poisoning. Its Preparation, Estimation and Stability

Cited by 66 publications

References 3 publications

The Metabolism of the Alkylphosphate Antagonists and its Pharmacologic Implications

The Metabolism of the Alkylphosphate Antagonists and its Pharmacologic Implications

Plasma concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration.

Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2‐PAM)

Contact Info

Product

Resources

About