Identification of neuronal target areas for nerve agents and specification of receptors for pharmacological treatment

Neurotoxicology
Trond Myhrer

Abstract

In order to shorten the list of candidate drugs with anticonvulsant potential against nerve agents, critical subreceptors in seizure controlling brain regions should be specified. Epileptiform activity does not spread randomly throughout the brain, but appears to be generated and propagated by specific anatomical routes. Nerve agents evoke seizure activity in the forebrain that progresses to the hind brain resulting in tonic-clonic convulsions. In some recent studies, it was shown that lesion of the area tempestas (AT), medial septum (MS), perirhinal cortex (PRC), or posterior piriform cortex (PPC) produces anticonvulsant effects (prevention of convulsions or delayed onset of convulsions) in rats exposed to soman, whereas damage to nucleus accumbens, nucleus basalis magnocellularis, amygdala, hippocampus, or entorhinal cortex does not cause anticonvulsant impact. These results are in compliance with findings that seizures can be generated in AT, MS, PRC, and PPC by means of nerve agents, chemoconvulsants, or kindling. Results from microinfusion studies show that anticonvulsant efficacy is obtained by GABA(A) modulators or cholinergic antagonists (M1-M5) in AT, cholinergic antagonists (M1-M5) in MS, combined glutamatergic (NMDA)...Continue Reading

Citations

Jun 15, 2011·Chemical Reviews·Kibong KimDavid G Churchill
Dec 15, 2015·Chemical Reviews·Yoon Jeong JangDavid G Churchill
Oct 8, 2011·Toxicology·Ben Avi Weissman, Lily Raveh
May 11, 2011·Toxicology Letters·Herman P M van HeldenIngrid H C Philippens
Jul 12, 2011·Pharmacology, Biochemistry, and Behavior·Krzysztof ŁukawskiStanisław J Czuczwar
Jul 10, 2012·Neurotoxicology·Jacob W SkoviraJohn H McDonough
Sep 12, 2013·European Journal of Pharmacology·Trond MyhrerPål Aas
Jun 4, 2016·Annals of the New York Academy of Sciences·Hilary S McCarren, John H McDonough
Oct 6, 2016·Critical Reviews in Toxicology·Mohamed B Abou-DoniaAshly Sobel Sokol
Oct 1, 2011·International Journal of Toxicology·Michael W PerkinsMadhusoodana P Nambiar

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