ArticleToxicology and applied pharmacology2014
A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides.
Article in Toxicology and applied pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 53 citations in OpenAlex.
- A Brain-Targeted Organophosphorus Hydrolase Fusion Protein Mediated by Angiopep-2 Neutralizes Central Organophosphates and Alleviates Neurotoxicity.International journal of nanomedicine · 2026Article
- L-carnitine: A novel approach in management of acute cholinesterase inhibitor insecticide poisoning.Toxicology research · 2024Article
- Reactivity of [(PNP)Mn(CO)ACS organic & inorganic Au · 2023Article
- Article
- Brain-targeting delivery of MMB4 DMS using carrier-free nanomedicine CRT-MMB4@MDZ.Drug delivery · 2021Article
- Positron emission tomography evaluation of oxime countermeasures in live rats using the tracer O-(2-[Annals of the New York Academy of Sciences · 2020Article
- Oxime-mediated reactivation of organophosphate-inhibited acetylcholinesterase with emphasis on centrally-active oximes.Neuropharmacology · 2020Review
- Organophosphorus compounds and oximes: a critical review.Archives of toxicology · 2020Review
- Acetylcholinesterase: The "Hub" for Neurodegenerative Diseases and Chemical Weapons Convention.Biomolecules · 2020Review
- Pharmacology, Pharmacokinetics, and Tissue Disposition of Zwitterionic Hydroxyiminoacetamido Alkylamines as Reactivating Antidotes for Organophosphate Exposure.The Journal of pharmacology and experimental therapeutics · 2018Article
- Evaluating the broad-spectrum efficacy of the acetylcholinesterase oximes reactivators MMB4 DMS, HLö-7 DMS, and 2-PAM Cl against phorate oxon, sarin, and VX in the Hartley guinea pig.Neurotoxicology · 2018Article
- The benefit of combinations of oximes for the ability of antidotal treatment to counteract sarin-induced brain damage in rats.BMC pharmacology & toxicology · 2018Article
- Kinetic analysis of oxime-assisted reactivation of human, Guinea pig, and rat acetylcholinesterase inhibited by the organophosphorus pesticide metabolite phorate oxon (PHO).Pesticide biochemistry and physiology · 2018Article
- Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor.Chemico-biological interactions · 2017Article
- The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats-A Comparison with Trimedoxime and the Oxime K203.Molecules (Basel, Switzerland) · 2017Article
- The role of oxidative stress in organophosphate and nerve agent toxicity.Annals of the New York Academy of Sciences · 2016Review
- Assessing the therapeutic efficacy of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig.The Journal of toxicological sciences · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl₂, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes.
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