Effect of HI-6, applied into the cerebral ventricles, on the inhibition of brain acetylcholinesterase by soman in rats.
When applied to rats (intraperitoneally) immediately after subcutaneous injection of soman (120 micrograms/kg) HI-6 (100 mg/kg) protected about 40% of the activity of acetylcholinesterase (AChE) in the motor end plate region of the diaphragm but did not protect AChE in the brain. However, a partial protection of AChE in brain against inhibition by soman was obtained in anaesthetized, atropinized rats by the oxime injected into the cerebral ventricle 5 min before parenteral exposure to soman. The AChE activity in brain of rats pretreated with HI-6, analyzed 60 min after the injection of soman was between 10 and 19%, while that in non-protected animals did not exceed 1% of the control. The degree of protection of AChE in brain was dose-dependent. Large doses of HI-6 (greater than or equal to 100 micrograms) were tolerated by animals because of the pentobarbital anaesthesia which counteracted the lethal action of HI-6. The rate of "aging" of AChE in brain inhibited by soman was analyzed by intracerebroventricular injection of 200 micrograms of HI-6 at different time intervals after the subcutaneous injection of soman. A statistically-significant reactivation of inhibited AChE activity in brain was demonstrated when HI-6 was applied up to 20 min after soman. The protection and reactivation by HI-6 of both AChE in brain and AChE in muscle end plates in poisoning with soman appear to be quite similar.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D010091:Oximes; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000037:antagonists & inhibitors*
D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; D000110:Acetylcholinesterase; C022870:asoxime chloride