A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
- Klíčová slova
- Acetylcholinesterase, K727, K733, oximes, sarin,
- MeSH
- acetylcholinesterasa krev chemie metabolismus MeSH
- antagonisté muskarinových receptorů terapeutické užití MeSH
- antidota terapeutické užití MeSH
- atropin terapeutické užití MeSH
- bránice účinky léků enzymologie MeSH
- cholinesterasové inhibitory aplikace a dávkování chemie toxicita MeSH
- kombinovaná farmakoterapie MeSH
- mozek účinky léků enzymologie MeSH
- myši MeSH
- neurony účinky léků enzymologie MeSH
- neurotoxické syndromy krev farmakoterapie etiologie metabolismus MeSH
- obidoxim chlorid terapeutické užití MeSH
- outbrední kmeny zvířat MeSH
- oximy terapeutické užití MeSH
- potkani Wistar MeSH
- proteiny nervové tkáně agonisté antagonisté a inhibitory metabolismus MeSH
- pyridinové sloučeniny terapeutické užití MeSH
- reaktivátory cholinesterázy terapeutické užití MeSH
- sarin aplikace a dávkování antagonisté a inhibitory toxicita MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 4-(ethylcarboxyl)-2'-(hydroxyiminomethyl)-1,1'-(phenylene-1,3-diyl)-bispyridinium MeSH Prohlížeč
- acetylcholinesterasa MeSH
- antagonisté muskarinových receptorů MeSH
- antidota MeSH
- asoxime chloride MeSH Prohlížeč
- atropin MeSH
- cholinesterasové inhibitory MeSH
- naphthylene-2,7-diyl-bis(2-hydroxyiminomethylpyridinium) MeSH Prohlížeč
- obidoxim chlorid MeSH
- oximy MeSH
- proteiny nervové tkáně MeSH
- pyridinové sloučeniny MeSH
- reaktivátory cholinesterázy MeSH
- sarin MeSH
The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel oximes K727 and K733 is significantly lower compared to the oxime HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.
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