Nerve agents anticonvulsants

Capacio BR, Harris LW, Anderson DR et al. (1992) Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. Drug Chem Toxicol 15 177-201 Dunham NW, Miya TS (1957) A note on a simple apparatus for detecting neurological deficit in mice and in rats. J Am Pharm Ass 46 208-209... 

Victims of certain chemical exposures will experience seizure activity. Patients must be protected from harm. Benzodiazepines are the mainstays in seizure treatment. Liberal doses are required titrate to effect. Termination of seizure activity may reflect onset of flaccid paralysis from the nerve agent rather than adequacy of anticonvulsant therapy. A bedside electroencephalograph (EEG) may be required to assess ongoing seizure activity. 

McDonough, J.H., Jr., Dochterman, L.W., Smith, C.D., Shih, T.M. (1995). Protection against nerve agent-induced neuropathology, but not cardiac pathology, is associated with the anticonvulsant action of drug treatment. Neurotoxicology 16 123-32. 

Enzymatic hydrolysis is a primary route for elimination of nerve agents. Specifically, treatment for OP intoxication includes atropine, a muscarinic receptor antagonist, an anticonvulsant such as diazepam, and a cholinesterase reactivator, an oxime. It has been found that drag-induced inhibition of ACh release and accumulation in the synaptic cleft, such as adenosine receptor antagonist early in the OP intoxication, improves the chances of survival. Some AChE reactivators, such as bispyridinum oximes, HI 6 and HLo 7 with atropine, are quite effective. 

Conventional anticonvulsant compounds have been reported to provide limited protection against nerve agent-induced seizures and muscle necrosis when given therapeutically (Lipp, 1972 Clinton et al, 1988). Sedation, tolerance, and abuse potential, however, limit prophylactic use of benzodiazepine compounds. 

Shih, T-M., McDonough, J.H. (2000). Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication. Arch. Toxicol. 74 165-72. 

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