Milosevic_1970_Br.J.Pharmacol_39_732

1. The effect of obidoxime on the rise in brain acetylcholine caused by the anticholinesterase paraoxon was studied in the rat.2. In animals poisoned with a sublethal dose of paraoxon and thereafter treated with obidoxime the levels of both "free" and total brain acetylcholine were practically the same as those in rats injected with paraoxon only.3. After poisoning with doses of paraoxon which are lethal unless an oxime is also given, the total acetylcholine in the brain of obidoxime-protected rats continued to accumulate, reaching a peak 2 h after injection of paraoxon. At this time no signs of central effects such as convulsions or tremor were seen.4. Atropine, given 30 min before paraoxon, markedly reduced the rise in total brain acetylcholine seen when the anticholinesterase is given alone.5. In rats pretreated with atropine and obidoxime excessive doses of paraoxon which are lethal in the absence of the antidotes produced a rise in total brain acetylcholine which was directly proportional to the dose of paraoxon administered.