Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.
Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit.
Pharmacology Department, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
Hilary S
HS
McCarren
Pharmacology Department, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
John H
JH
McDonough
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D000067397:Nerve Agents / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000188:drug therapy*
D000927:Anticonvulsants; D000067397:Nerve Agents; D009943:Organophosphorus Compounds; D010575:Pesticides
anticonvulsant; nerve agent; organophosphate; pesticide; status epilepticus