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.

• Keywords
• CB7, K027, acetylcholinesterase, antidote, cucurbit[7]uril, cucurbiturils, in vivo, mouse, paraoxon, pesticide,
• MeSH
• Atropine chemistry   MeSH
• Blood-Brain Barrier MeSH
• Imidazoles chemistry   MeSH
• Mice MeSH
• Oximes chemistry   MeSH
• Paraoxon chemistry   toxicity   MeSH
• Computer Simulation MeSH
• Bridged-Ring Compounds chemistry   MeSH
• Pyridinium Compounds chemistry   MeSH
• Cholinesterase Reactivators chemistry   toxicity   MeSH
• Molecular Docking Simulation MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide MeSH Browser
• Atropine MeSH
• cucurbit(7)uril MeSH Browser
• Imidazoles MeSH
• Oximes MeSH
• Paraoxon MeSH
• Bridged-Ring Compounds MeSH
• Pyridinium Compounds MeSH
• Cholinesterase Reactivators MeSH