Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.

Abstract:

: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.

journal_name

Ann N Y Acad Sci

authors

McCarren HS,McDonough JH Jr

doi

10.1111/nyas.13092

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

144-50

issue

1

eissn

0077-8923

issn

1749-6632

journal_volume

1374

pub_type

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