Nerve Gas Antidotes

Organophosphorus nerve gases such as sarin, soman and VX act mainly by inhibiting cholinesterase at cholinergic synapses. The consequent accumulation of acetylcholine results in muscle twitching, glandular hypersecretion and cognitive and mood effects. High doses cause seizures and death from respiratory failure. Nerve agents affect both main types of cholinergic receptor--muscarinic and nicotinic. Treatment of nerve agent poisoning at present relies on two approaches. In the first, an oxime is given to detach the agent from cholinesterase, thus reactivating the enzyme. This mitigates both nicotinic and muscarinic effects, for those nerve agents against which oximes are effective (which do not include soman). In the second, the muscarinic antagonist atropine is used to quell the effects of excessive acetylcholine action. Atropine is of special value when the nerve agent is oxime-resistant or when symptoms are already severe. However, atropine targets only excessive muscarinic activity.