MK-801 protects against seizures induced by the cholinesterase inhibitor soman.

MK-801, a novel anticonvulsant which is a potent N-methyl-d-aspartate antagonist, attenuated or blocked seizures and convulsions induced by the irreversible organophosphorus anticholinesterase inhibitor soman. Guinea pigs chronically instrumented for electrocorticogram recording were given a low dose (1 mg/kg) or a high dose (5 mg/kg) of MK-801 or saline vehicle 30 min prior to receiving 2 x LD50 of soman. All animals were treated with atropine methylnitrate and pralidoxime chloride 30 sec after soman injection. All saline control subjects exhibited severe seizures and convulsions shortly after receiving soman. Low dose MK-801 greatly attenuated and high dose MK-801 completely blocked seizure activity. Animals treated with MK-801 recovered faster and had a much greater probability of survival for 48 hr after soman exposure than did controls. This is the first demonstration of the involvement of the excitatory amino acid neurotransmitter system in seizures and convulsions induced by a cholinesterase inhibitor.