Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood-brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC-pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks.

• Klíčová slova
• CB7, K027, acetylcholinesterase, antidote, cucurbit[7]uril, cucurbiturils, in vivo, mouse, paraoxon, pesticide,
• MeSH
• atropin chemie   MeSH
• hematoencefalická bariéra MeSH
• imidazoly chemie   MeSH
• myši MeSH
• oximy chemie   MeSH
• paraoxon chemie   toxicita   MeSH
• počítačová simulace MeSH
• přemostěné cyklické sloučeniny chemie   MeSH
• pyridinové sloučeniny chemie   MeSH
• reaktivátory cholinesterasy chemie   toxicita   MeSH
• simulace molekulového dockingu MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide MeSH Prohlížeč
• atropin MeSH
• cucurbit(7)uril MeSH Prohlížeč
• imidazoly MeSH
• oximy MeSH
• paraoxon MeSH
• přemostěné cyklické sloučeniny MeSH
• pyridinové sloučeniny MeSH
• reaktivátory cholinesterasy MeSH