Targeting the glutamatergic system to counteract organophosphate poisoning: A novel therapeutic strategy

Neurobiology of Disease
Vassiliki Aroniadou-AnderjaskaMaria F M Braga

Abstract

One of the devastating effects of acute exposure to organophosphates, like nerve agents, is the induction of severe and prolonged status epilepticus (SE), which can cause death, or brain damage if death is prevented. Seizures after exposure are initiated by muscarinic receptor hyperstimulation-after inhibition of acetylcholinesterase by the organophosphorus agent and subsequent elevation of acetylcholine-but they are reinforced and sustained by glutamatergic hyperexcitation, which is the primary cause of brain damage. Diazepam is the FDA-approved anticonvulsant for the treatment of nerve agent-induced SE, and its replacement by midazolam is currently under consideration. However, clinical data derived from the treatment of SE of any etiology, as well as studies on the control of nerve agent-induced SE in animal models, have indicated that diazepam and midazolam control seizures only temporarily, their antiseizure efficacy is reduced as the latency of treatment from the onset of SE increases, and their neuroprotective efficacy is limited or absent. Here, we review data on the discovery of a novel anticonvulsant and neuroprotectant, LY293558, an AMPA/GluK1 receptor antagonist. Treatment of soman-exposed immature, young-adult, and...Continue Reading

References

Sep 1, 1979·Archives of Neurology·R E RamsayB J Wilder
Nov 1, 1991·Experimental Neurology·D F WozniakJ W Olney
Aug 1, 1995·Developmental Medicine and Child Neurology·R AppletonE Molyneux
Feb 16, 1993·European Journal of Pharmacology·R L HudkinsD L DeHaven-Hudkins
Nov 14, 1997·Neuroscience and Biobehavioral Reviews·J H McDonough, T M Shih
Oct 7, 1998·Epilepsy Research·A PitkänenT Salmenperä
Oct 28, 1998·Journal of Physiology, Paris·G LallementG Blanchet
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·A Rodríguez-MorenoJ Lerma
May 23, 2001·Nature Neuroscience·H LiM A Rogawski
Mar 29, 2002·Journal of Applied Toxicology : JAT·I KoplovitzJ McDonough
Apr 16, 2002·Journal of Child Neurology·Sunit SinghiM Jayashree
Apr 15, 2003·Toxicology and Applied Pharmacology·Tsung-Ming ShihJohn H McDonough
May 2, 2003·Annals of the New York Academy of Sciences·Anantha ShekharDonald G Rainnie
Jul 2, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lily RavehBen Avi Weissman
Jul 31, 2003·Epilepsia·Howard P GoodkinGregory L Holmes
Mar 20, 2004·The Journal of Pharmacology and Experimental Therapeutics·Patrick K HarrisonJohn E H Tattersall
May 29, 2004·Neuropharmacology·Julia C A MoreDavid E Jane
Jun 16, 2004·Cephalalgia : an International Journal of Headache·C N SangF Vandenhende
Jun 10, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Howard P GoodkinJaideep Kapur
Aug 27, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David E NaylorClaude G Wasterlain
Jun 20, 2006·British Journal of Pharmacology·Claudia Campo-SoriaDavid S Weiss
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yitao LiuYu Tian Wang
Apr 17, 2007·International Review of Neurobiology·Alan R Towne
Jan 5, 2008·Handbook of Experimental Pharmacology·K T Olkkola, J Ahonen
Jan 30, 2008·Epilepsy Research·Vassiliki Aroniadou-AnderjaskaMaria F M Braga
Feb 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David Fernández de SevillaWashington Buño
Mar 6, 2008·Toxicology and Applied Pharmacology·Lily RavehRachel Brandeis
Jul 29, 2008·Neuropharmacology·Graham L CollingridgeMichael Spedding
Sep 17, 2008·Neuropharmacology·David E JaneGraham L Collingridge
Jan 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joyce Wondolowski, Matthew Frerking
Apr 28, 2009·Nature·Vikaas S SohalKarl Deisseroth
May 12, 2009·Neuroscience Letters·Robert E BlairRobert J DeLorenzo

❮ Previous
Next ❯

Citations

Apr 3, 2020·Annals of the New York Academy of Sciences·Marcio De Araujo FurtadoMaria F M Braga
Jul 27, 2021·Current Opinion in Toxicology·Yi-Hua Tsai, Pamela J Lein

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.