A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase
Abstract Background Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. Methods To determine if this reactivating efficacy would extend...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-02-01
|
| Series: | BMC Pharmacology and Toxicology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40360-018-0196-3 |
| _version_ | 1819046522165133312 |
|---|---|
| author | Kamil Kuca Kamil Musilek Daniel Jun Jana Zdarova-Karasova Eugenie Nepovimova Ondrej Soukup Martina Hrabinova John Mikler Tanos C. C. Franca Elaine F. F. Da Cunha Alexandre A. De Castro Martin Valis Teodorico C. Ramalho |
| author_facet | Kamil Kuca Kamil Musilek Daniel Jun Jana Zdarova-Karasova Eugenie Nepovimova Ondrej Soukup Martina Hrabinova John Mikler Tanos C. C. Franca Elaine F. F. Da Cunha Alexandre A. De Castro Martin Valis Teodorico C. Ramalho |
| author_sort | Kamil Kuca |
| collection | DOAJ |
| description | Abstract Background Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. Methods To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k r) of 2142 min− 1. M− 1, which was 51 times higher than that obtained for obidoxime (k r = 42 min− 1. M− 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. Discussion According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure. |
| first_indexed | 2024-12-21T10:45:48Z |
| format | Article |
| id | doaj.art-ba8425cd990247f4bd02fb26adefa794 |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-12-21T10:45:48Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-ba8425cd990247f4bd02fb26adefa7942022-12-21T19:06:49ZengBMCBMC Pharmacology and Toxicology2050-65112018-02-0119111010.1186/s40360-018-0196-3A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesteraseKamil Kuca0Kamil Musilek1Daniel Jun2Jana Zdarova-Karasova3Eugenie Nepovimova4Ondrej Soukup5Martina Hrabinova6John Mikler7Tanos C. C. Franca8Elaine F. F. Da Cunha9Alexandre A. De Castro10Martin Valis11Teodorico C. Ramalho12Biomedical Research Center, University Hospital Hradec KraloveBiomedical Research Center, University Hospital Hradec KraloveBiomedical Research Center, University Hospital Hradec KraloveBiomedical Research Center, University Hospital Hradec KraloveBiomedical Research Center, University Hospital Hradec KraloveBiomedical Research Center, University Hospital Hradec KraloveBiomedical Research Center, University Hospital Hradec KraloveDefence Research and Development Canada - Suffield Research Centre, Department of National Defence, SuffieldCenter for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec KraloveDepartment of Chemistry, Federal University of LavrasDepartment of Chemistry, Federal University of LavrasNeurology Clinic, University Hospital Hradec KraloveCenter for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec KraloveAbstract Background Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. Methods To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k r) of 2142 min− 1. M− 1, which was 51 times higher than that obtained for obidoxime (k r = 42 min− 1. M− 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. Discussion According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.http://link.springer.com/article/10.1186/s40360-018-0196-3AntidotesChemical warfare agentsPoisoningTreatmentReactivatorOxime |
| spellingShingle | Kamil Kuca Kamil Musilek Daniel Jun Jana Zdarova-Karasova Eugenie Nepovimova Ondrej Soukup Martina Hrabinova John Mikler Tanos C. C. Franca Elaine F. F. Da Cunha Alexandre A. De Castro Martin Valis Teodorico C. Ramalho A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase BMC Pharmacology and Toxicology Antidotes Chemical warfare agents Poisoning Treatment Reactivator Oxime |
| title | A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase |
| title_full | A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase |
| title_fullStr | A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase |
| title_full_unstemmed | A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase |
| title_short | A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase |
| title_sort | newly developed oxime k203 is the most effective reactivator of tabun inhibited acetylcholinesterase |
| topic | Antidotes Chemical warfare agents Poisoning Treatment Reactivator Oxime |
| url | http://link.springer.com/article/10.1186/s40360-018-0196-3 |
| work_keys_str_mv | AT kamilkuca anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT kamilmusilek anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT danieljun anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT janazdarovakarasova anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT eugenienepovimova anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT ondrejsoukup anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT martinahrabinova anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT johnmikler anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT tanosccfranca anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT elaineffdacunha anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT alexandreadecastro anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT martinvalis anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT teodoricocramalho anewlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT kamilkuca newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT kamilmusilek newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT danieljun newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT janazdarovakarasova newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT eugenienepovimova newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT ondrejsoukup newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT martinahrabinova newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT johnmikler newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT tanosccfranca newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT elaineffdacunha newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT alexandreadecastro newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT martinvalis newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase AT teodoricocramalho newlydevelopedoximek203isthemosteffectivereactivatoroftabuninhibitedacetylcholinesterase |