Failure of Toxogonin to Reactivate Soman-Inhibited Brain AChE in Monkeys and Regeneration of the Enzyme.
Technical rept. Aug 68-Aug 71,
EDGEWOOD ARSENAL MD
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Administration of Toxogonin to monkeys intoxicated with pinacolyl methylphosphonofluoridate Soman did not result in significant reactivation P 0.05 of inhibited acetylcholinesterase AChE. Aging, i.e., refractoriness of reactivation due to rapid dealkylation of the Soman-inhibited enzyme, can be minimized if inhibition of AChE is carried out at pH 8.8 and 0C. Nevertheless, addition of .00005 M Toxogonin, a concentration which could be expected from a physiologically acceptable dosage in vivo, did not result in reactivation of unaged, inhibited AChE. Therefore, aging and inability of the oxime to cross the blood-brain barrier are of secondary importance in the failure of Toxogonin to reactivate brain AChE inhibited by Soman. Another part of this study concerned the temporal relationship between the persistent central depression of respiration seen in monkeys after poisoning with Soman and the degree of inhibition of brain AChE. Inasmuch as the AChE activity of the pons and medulla shows significant regeneration within 72 hours, prolonged respiratory depression cannot be attributed to a stationary, depressed enzyme level of these parts of the brain. Author