A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with presently used oximes and H oximes against sarin by in vitro and in vivo methods.
1. The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium/- 2-butene dibromide), against organophosphate sarin was compared with presently used oximes (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) by in vitro and in vivo methods. 2. Our results confirm that the new oxime BI-6 is a significantly more efficacious acetylcholinesterase reactivator than currently available pralidoxime and obidoxime but not as effective as H oximes (HI-6, HLö-7) in vitro as well as in vivo. In addition, the oxime BI-6 is able to protect supralethal sarin poisoned rats at human-relevant doses. 3. Our data also suggest that the potency of oximes tested to reactivate sarin-inhibited acetylcholinesterase in vitro closely corresponds to their reactivating efficacy in vivo and their ability to protect rats poisoned with supralethal doses of sarin.
Kassa
J
J
Purkyne Military Medical Academy, Hradec Králové, Czech Republic.
Cabal
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D003964:Diaphragm / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D007928:Lethal Dose 50; D008297:Male; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000517:prevention & control; D010091:Oximes / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000633:toxicity*
C118647:BI 6; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D012524:Sarin