REM-SLEEP PATHWAYS AND ANTICHOLINESTERASE INTOXICATION - A MECHANISM FOR NERVE AGENT-INDUCED, CENTRAL RESPIRATORY-FAILURE

The mechanism of death following exposure to anticholinesterases, such as the highly toxic nerve agents soman and VX, and other organophosph ate anticholinesterases such as the insecticide parathion, remains unc lear, although evidence from nerve agent research suggests that death occurs by an atropine blockable respiratory failure mediated through m echanisms involving the central nervous system. It is proposed that RE M sleep pathways, which can be triggered by acetylcholine accumulation in the pontomedullar reticular field, mediate respiratory failure thr ough the inhibition of respiratory muscles. Cholinergic activation of REM sleep activities may also account for other physiological and beha vioural effects that follow exposure to nerve agents. These include fo rebrain activation, which is associated with EEG desynchronization and seizures, locomotor depression with concomitant loss of righting refl ex, and limb jerks and extensions. Pharmacologic evidence for atropine and clonidine protection against soman intoxication effects is entire ly consistent with a scenario of cholinergic receptor activation in th e pontomedullar reticular field.