REM sleep pathways and anticholinesterase intoxication: a mechanism for nerve agent-induced, central respiratory...

The mechanism of death following exposure to anticholinesterases, such as the highly toxic nerve agents soman and VX, and other organophosphate anticholinesterases such as the insecticide parathion, remains unclear, although evidence from nerve agent research suggests that death occurs by an atropine blockable respiratory failure mediated through mechanisms involving the central nervous system. It is proposed that REM sleep pathways, which can be triggered by acetylcholine accumulation in the pontomedullar reticular field, mediate respiratory failure through the inhibition of respiratory muscles. Cholinergic activation of REM sleep activities may also account for other physiological and behavioural effects that follow exposure to nerve agents. These include forebrain activation, which is associated with EEG desynchronization and seizures, locomotor depression with concomitant loss of righting reflex, and limb jerks and extensions. Pharmacologic evidence for atropine and clonidine protection against soman intoxication effects is entirely consistent with a scenario of cholinergic receptor activation in the pontomedullar reticular field.