{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:06:39Z","timestamp":1790838399967,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006021","name":"Direction G\u00e9n\u00e9rale de l\u2019Armement","doi-asserted-by":"publisher","award":["PDH-2-NRBC-4-C-4203"],"award-info":[{"award-number":["PDH-2-NRBC-4-C-4203"]}],"id":[{"id":"10.13039\/501100006021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006021","name":"Direction G\u00e9n\u00e9rale de l\u2019Armement","doi-asserted-by":"publisher","award":["PDH-5-C-4210"],"award-info":[{"award-number":["PDH-5-C-4210"]}],"id":[{"id":"10.13039\/501100006021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-CE39-0012"],"award-info":[{"award-number":["ANR-17-CE39-0012"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["LABEX ANR-10-LABX-0034_Medalis"],"award-info":[{"award-number":["LABEX ANR-10-LABX-0034_Medalis"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>(1) Background: Human exposure to organophosphorus compounds employed as pesticides or as chemical warfare agents induces deleterious effects due to cholinesterase inhibition. One therapeutic approach is the reactivation of inhibited acetylcholinesterase by oximes. While currently available oximes are unable to reach the central nervous system to reactivate cholinesterases or to display a wide spectrum of action against the variety of organophosphorus compounds, we aim to identify new reactivators without such drawbacks. (2) Methods: This study gathers an exhaustive work to assess in vitro and in vivo efficacy, and toxicity of a hybrid tetrahydroacridine pyridinaldoxime reactivator, KM297, compared to pralidoxime. (3) Results: Blood\u2013brain barrier crossing assay carried out on a human in vitro model established that KM297 has an endothelial permeability coefficient twice that of pralidoxime. It also presents higher cytotoxicity, particularly on bone marrow-derived cells. Its strong cholinesterase inhibition potency seems to be correlated to its low protective efficacy in mice exposed to paraoxon. Ventilatory monitoring of KM297-treated mice by double-chamber plethysmography shows toxic effects at the selected therapeutic dose. This breathing assessment could help define the No Observed Adverse Effect Level (NOAEL) dose of new oximes which would have a maximum therapeutic effect without any toxic side effects.<\/jats:p>","DOI":"10.3390\/biom10060858","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:32:21Z","timestamp":1591327941000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Efficacy Assessment of an Uncharged Reactivator of NOP-Inhibited Acetylcholinesterase Based on Tetrahydroacridine Pyridine-Aldoxime Hybrid in Mouse Compared to Pralidoxime"],"prefix":"10.3390","volume":"10","author":[{"given":"Andr\u00e9-Guilhem","family":"Calas","sequence":"first","affiliation":[{"name":"D\u00e9partement de Toxicologie et Risques Chimiques, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, F-91220 Br\u00e9tigny-sur-Orge, France"},{"name":"COGNition and ACtion Group, UMR 8257, CNRS-MD-UPV, Centre universitaire des Saints-P\u00e8res, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Hanak","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Toxicologie et Risques Chimiques, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, F-91220 Br\u00e9tigny-sur-Orge, France"},{"name":"COGNition and ACtion Group, UMR 8257, CNRS-MD-UPV, Centre universitaire des Saints-P\u00e8res, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Jaffr\u00e9","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Toxicologie et Risques Chimiques, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, F-91220 Br\u00e9tigny-sur-Orge, France"},{"name":"COGNition and ACtion Group, UMR 8257, CNRS-MD-UPV, Centre universitaire des Saints-P\u00e8res, F-75006 Paris, 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