Central activity of acetylcholinesterase oxime reactivators.
The ability of various oximes to antagonize the sarin-induced hypothermia and reactivate phosphorylated acetylcholinesterase was used as an indicator of the central activity of oximes. HI-6, but neither toxogonin nor PAM Cl, antagonized sarin-induced hypothermia and reactivated brain acetylcholinesterase, in particular hypothalamic acetylcholinesterase. The sarin-induced hypothermia appears to be a muscarinic cholinergic action since atropine was also an effective antagonist of sarin-induced hypothermia. Neither HI-6 nor toxogonin antagonized oxotremorine-induced hypothermia, indicating that these oximes do not possess central cholinolytic activity. The results demonstrated that HI-6 penetrated the blood-brain barrier in a sufficient concentration to produce a biochemical and physiological action against sarin poisoning.
Clement
J G
JG
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D006624:Hippocampus / Q000201:enzymology; D007031:Hypothalamus / Q000201:enzymology; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010091:Oximes / Q000494:pharmacology*; D010766:Phosphorylation; D012524:Sarin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D012524:Sarin; D000110:Acetylcholinesterase