ArticleAnnals of the New York Academy of Sciences2016
Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates.
Article in Annals of the New York Academy of Sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Dual targeting of iNOS and Src tyrosine kinase as a superior therapeutic strategy against soman-induced long-term neurotoxicity: multimodal biomarker, imaging, and neurobehavioral outcome analyses.Acta neuropathologica communications · 2026Article
- Challenges and advances in the development of antidotes against A-series nerve agents.Archives of toxicology · 2026Review
- The in silico identification of novel broad-spectrum antidotes for poisoning by organophosphate anticholinesterases.Journal of computer-aided molecular design · 2023Article
- The in silico identification of novel broad-spectrum antidotes for poisoning by organophosphate anticholinesterases.Research square · 2023Article
- Ophthalmic manifestations and management considerations for emerging chemical threats.Frontiers in toxicology · 2023Review
- A rapidFrontiers in cellular neuroscience · 2022Article
- Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach.Scientific reports · 2021Article
- Non-quaternary oximes detoxify nerve agents and reactivate nerve agent-inhibited human butyrylcholinesterase.Communications biology · 2021Article
- Novel pyridinium oximes enhance 24-h survivability against a lethal dose of nerve agent surrogate in adult female rats.Toxicology · 2020Article
- Structure Dependent Determination of Organophosphate Targets in Mammalian Tissues Using Activity-Based Protein Profiling.Chemical research in toxicology · 2020Article
- Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review.RSC advances · 2020Review
- Novel centrally active oxime reactivators of acetylcholinesterase inhibited by surrogates of sarin and VX.Neurobiology of disease · 2020Review
- Positron emission tomography studies of organophosphate chemical threats and oxime countermeasures.Neurobiology of disease · 2020Review
- Acute Toxic Injuries of Rat's Visceral Tissues Induced by Different Oximes.Scientific reports · 2019Article
- Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Review
- Molecular Modeling and In Vitro Studies of a Neutral Oxime as a Potential Reactivator for Acetylcholinesterase Inhibited by Paraoxon.Molecules (Basel, Switzerland) · 2018Article
- The inhibition, reactivation and mechanism of VX-, sarin-, fluoro-VX and fluoro-sarin surrogates following their interaction with HuAChE and HuBuChE.Chemico-biological interactions · 2018Article
- Responding to chemical weapons violations in Syria: legal, health, and humanitarian recommendations.Conflict and health · 2018Review
- Toxic chemical weapons of assassination and warfare: nerve agents VX and sarin.Toxicology communications · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain.
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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.