Accession Number ADA583974
Title M Current-Based Therapies for Nerve Agent Seizures.
Publication Date Jul 2013
Media Count 47p
Personal Author J. Kapur J. Williamson J. L. Sun M. Todorovic T. Zhang
Abstract This is a proposal to develop novel, mechanism-based therapies for the treatment of organophosphate (OP) nerve agent-induced seizures. The primary goal of this proposal is to test two interrelated hypotheses: (1) Cholinergic nerve agents cause neuronal hyper-excitability by inhibiting M/KCNQ2/3 potassium channels. (2) Cholinergic seizures can be blocked by drugs that can open potassium channels mediating M currents. These hypotheses will be tested by accomplishing three aims. (Aim 1) To test whether modulation of M channel modulators (antagonists and openers) glutamatergic transmission on CA1 pyramidal neurons and dentate granule cells; (Aim 2) To characterize the effects of M current enhancers on excitabtility and bursting of CA1 pyramidal neurons; (Aim 3) To test anticonvulsant action of three M-Channel openers in cholinergic overstimulation-induced status epilepticus.
Keywords Augmentation
Cholinergic nerves
Convulsive disorders
M channels
Nerve agents
Nerve cells
Parasympatholytic agents
Test and evaluation

Source Agency Non Paid ADAS
NTIS Subject Category 74D - Chemical, Biological, & Radiological Warfare
99A - Analytical Chemistry
92B - Psychology
Corporate Author Virginia Univ., Charlottesville.
Document Type Technical report
Title Note Final rept. 1 Jul 2010-30 Jun 2013.
NTIS Issue Number 1402
Contract Number W81XWH-10-1-0491

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