Action of Cholinergic Poisons on the Central Nervous System and Effectiveness of Potential Antidotes

摘要

The aims were to identify the effects of soman on rat brain and the extent of protection by antidotes atropine, benactyzine, scopolamine, physostigmine, physostigmine, pyridostigmine, mecamylamine, pralidoxime, diazepam. The behavior, local cerebral glucose use (LCGU), brain muscarinic receptors and histology were studied for both seizure phase (1 hr after exposure) and neuropathology phase (72 hr after exposure). As we reported previously, soman induces prolonged convulsions associated with large LCGU increases in many brain regions and loss of LCGU in others. This report provides the quantitative date of LCGU for 46 brain regions in rats pretreated with 2 different doses of 7 different antidotes prior to exposure to soman. The values are given for the seizure and the neuropathology phases. The LCGU changes induced by DFP are contrasted with those induced by soman. Also, brain regional muscarinic receptor changes following convulsant doses of kainic acid and of soman are described. Under the conditions of these experiments, the muscarinic blockers scopolamine and benactyzine and the 'reversible' acetylcholinesterase inhibitor, physostigmine were the most effective of the antidotes studied.