HI-6: reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the rat.
HI-6, ([[[(4-aminocarbonyl)pyridino]methoxy]methyl]-2-] (hydroxyimino)methyl]-pyridinium dichloride), is an oxime which, when combined with atropine, is an extremely effective therapy against organophosphate poisoning. It was found that, following soman (287 micrograms/kg) poisoning, HI-6 reactivated acetylcholinesterase in the diaphragm and intercostal muscles but not in the brain. At a lower dose of soman (110 micrograms/kg), HI-6 reactivated sarin-inhibited acetylcholinesterase in the brain and in the respiratory musculature but did not reactivate tabun-inhibited acetylcholinesterase. It was also found that soman produced a differential inhibition  of diaphragm and intercostal muscle acetylcholinesterase in vivo, whereas the in vitro I50 for soman was the same in both areas. HI-6 was capable of reactivating soman-inhibited acetylcholinesterase when administered up to 30 min post-soman, indicating that the rate of aging of the soman-acetylcholinesterase complex is slower than previously reported. The above results suggest that, in severe soman poisoning, the primary lesion occurs in peripheral acetylcholinesterase in the respiratory musculature (specifically the diaphragm).
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators; D008297:Male; D010755:Organophosphates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010091:Oximes; D010525:Peripheral Nerves / Q000201:enzymology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012524:Sarin / Q000494:pharmacology; D012999:Soman / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; D012524:Sarin; D000110:Acetylcholinesterase; C022870:asoxime chloride; C009374:tabun