ReviewNeurobiology of disease2020
Novel centrally active oxime reactivators of acetylcholinesterase inhibited by surrogates of sarin and VX.
Review in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Kinetic and structural evidence for specific DMSO interference with reversible binding of uncharged bis-oximes to hAChE and their reactivation kinetics of OP-hAChE.Chemico-biological interactions · 2025Article
- Article
- Pharmacokinetics of three novel pyridinium aldoxime acetylcholinesterase reactivators in female rats.Toxicology and applied pharmacology · 2022Article
- Long-Term Anxiety-like Behavior and Microbiota Changes Induced in Mice by Sublethal Doses of Acute Sarin Surrogate Exposure.Biomedicines · 2022Article
- A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning.Journal of medicinal chemistry · 2022Article
- FDA-Approved Oximes and Their Significance in Medicinal Chemistry.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Novel pyridinium oximes enhance 24-h survivability against a lethal dose of nerve agent surrogate in adult female rats.Toxicology · 2020Article
- Central neuroprotection demonstrated by novel oxime countermeasures to nerve agent surrogates.Annals of the New York Academy of Sciences · 2020Review
- Understanding the Interaction Modes and Reactivity of Trimedoxime towardInternational journal of molecular sciences · 2020Article
- Acetylcholinesterase inhibition resulting from exposure to inhaled OP can be prevented by pretreatment with BChE in both macaques and minipigs.Neuropharmacology · 2020Review
- Organophosphorus compounds and oximes: a critical review.Archives of toxicology · 2020Review
- Rational design, synthesis, and evaluation of uncharged, "smart" bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase.The Journal of biological chemistry · 2020Article
- Preface: Discovery and development of better medical countermeasures for chemical threats targeting the nervous system.Neurobiology of disease · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A novel oxime platform, the substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937), was invented at Mississippi State University with an objective of discovering a brain-penetrating antidote to highly potent organophosphate anticholinesterases, such as the nerve agents. The goal was reactivation of inhibited brain acetylcholinesterase to attenuate the organophosphate-induced hypercholinergic activity that results in glutamate-mediated excitotoxicity and neuropathology. The currently approved oxime antidote in the US, 2-PAM, cannot do this. Using highly relevant surrogates of sarin and VX that leave acetylcholinesterase phosphylated with the same chemical moiety as their respective nerve agents, in vitro screens and in vivo tests in rats were conducted to identify the most efficacious members of this platform. The most promising novel oximes provided 24-h survival of lethal level surrogate exposure better than 2-PAM in almost all cases, and two of the oximes shortened the time to cessation of seizure-like behavior while 2-PAM did not. The most promising novel oximes attenuated neuropathology as indicated by immunohistochemical stains for both glia and neurons, while 2-PAM did not protect either glia or neurons. These results strongly suggest that these novel oximes can function within the brain to protect it, and therefore show great promise as potential future nerve agent antidotes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.