ArticleChemico-biological interactions2017
Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor.
Article in Chemico-biological interactions, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Next-generation broad-spectrum reactivators for effective countermeasure against organophosphorus poisoning.Archives of toxicology · 2026Article
- Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Strategies for enhanced bioavailability of oxime reactivators in the central nervous system.Archives of toxicology · 2023Review
- The impact of solvents on the toxicity of the banned parathion insecticide.Chemico-biological interactions · 2023Article
- Enhancing Target Tissue Levels and Diminishing Plasma Clearance of Ionizing Zwitterionic Antidotes in Organophosphate Exposures.The Journal of pharmacology and experimental therapeutics · 2021Article
- Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach.Scientific reports · 2021Article
- Development of versatile and potent monoquaternary reactivators of acetylcholinesterase.Archives of toxicology · 2021Article
- Counteracting poisoning with chemical warfare nerve agents.Arhiv za higijenu rada i toksikologiju · 2020Review
- Positron emission tomography evaluation of oxime countermeasures in live rats using the tracer O-(2-[Annals of the New York Academy of Sciences · 2020Article
- Central neuroprotection demonstrated by novel oxime countermeasures to nerve agent surrogates.Annals of the New York Academy of Sciences · 2020Review
- Methyl Scanning and Revised Binding Mode of 2-Pralidoxime, an Antidote for Nerve Agent Poisoning.ACS medicinal chemistry letters · 2020Article
- Oxime-mediated reactivation of organophosphate-inhibited acetylcholinesterase with emphasis on centrally-active oximes.Neuropharmacology · 2020Review
- 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
- Evaluation of high-affinity phenyltetrahydroisoquinoline aldoximes, linked through anti-triazoles, as reactivators of phosphylated cholinesterases.Toxicology letters · 2020Article
- Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review.RSC advances · 2020Review
- Pharmacology, Pharmacokinetics, and Tissue Disposition of Zwitterionic Hydroxyiminoacetamido Alkylamines as Reactivating Antidotes for Organophosphate Exposure.The Journal of pharmacology and experimental therapeutics · 2018Article
- Post-exposure treatment with the oxime RS194B rapidly reactivates and reverses advanced symptoms of lethal inhaled paraoxon in macaques.Toxicology letters · 2018Article
- Paraoxon: An Anticholinesterase That Triggers an Excitotoxic Cascade of Oxidative Stress, Adhesion Responses, and Synaptic Compromise.European scientific journal · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Organophosphate (OP) nerve agents and pesticides trigger a common mechanism of neurotoxicity resulting from critical targeting and inhibition of acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Therapeutic countermeasures have thus focused on either administering an oxime post-exposure, that can rapidly reactivate OP-inhibited AChE, or by preventing OP poisoning through administering pre-exposure treatments that scavenge OPs before they inhibit their physiological AChE targets. While several pyridinium aldoxime antidotes are currently approved, their utility is impaired due to their inability to cross the blood-brain barrier (BBB) efficiently. The present study utilized a macaque (Ma) model to demonstrate the efficacy of a novel zwitterionic and centrally acting oxime RS194B to reactivate sarin- and paraoxon-inhibited macaque AChE and butyrylcholinesterase (BChE) in vitro and to further assess the capacity of RS194B to effect a reversal of clinical symptoms following sarin inhalation in vivo. In vitro, oxime reactivation of MaAChE and MaBChE was shown to be comparable to their human orthologs, while the macaque studies indicated that IM administration of 62.5 mg/kg of RS194B and 0.28 mg/kg atropine after continuous exposure to 49.6 μg/kg sarin vapor, rapidly reactivated the inhibited AChE and BChE in blood and reversed both early and advanced clinical symptoms of sarin-induced toxicity following pulmonary exposure within 1 h. The rapid cessation of autonomic and central symptoms, including convulsions, observed in macaques bodes well for the use of RS194B as an intra- or post-exposure human treatment and validates the macaque model in generating efficacy and toxicology data required for approval under the FDA Animal rule.
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