PMID: 11907154Mar 22, 2002Paper

Prevention of in vivo excitotoxicity by a family of trialkylglycines, a novel class of neuroprotectants

The Journal of Pharmacology and Experimental Therapeutics
Carmina MontoliuVicente Felipo

Abstract

Excitotoxicity has been implicated in the etiology of ischemic stroke and chronic neurodegenerative disorders. Hence, the development of novel neuroprotectant molecules that ameliorate excitotoxic brain damage is vigorously pursued. We used a neuroprotection-based cellular assay to screen a synthetic combinatorial library of N-alkylglycine trimers. Two compounds (6-1-2 and 6-1-10) that efficiently prevented excitotoxic neurodegeneration in vitro and in vivo were identified. Both molecules protected primary cultures of cerebellar neurons against glutamate-induced neuronal death with an efficiency equivalent to N-methyl-D-aspartate (NMDA) receptor antagonists. These trialkylglycines did not block appreciably the NMDA receptor channel, or attenuated glutamate-induced increase of Ca(2+), or affect the glutamate-nitric oxide-cGMP pathway. Intraperitoneal injection of both peptoids in mice attenuated > or = 80% ammonia-induced, NMDA receptor-mediated animal death. Furthermore, these two molecules reduced by > or = 50% the neurodegeneration in striatum in a rat model of cerebral ischemia. Neuroprotection against ischemia was associated with decreased activation of caspase-3, reflecting prevention of apoptotic neuronal death. Collectiv...Continue Reading

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Citations

Jan 1, 2003·Current Neurology and Neuroscience Reports·Bruce OvbiageleJeffrey L Saver
Feb 1, 2011·Brain Research·Richard M BlissJean Strahlendorf
Aug 18, 2009·Brain Research Bulletin·Birgit NimmervollHubert H Kerschbaum
May 27, 2008·Neuroscience Letters·Tinna M RossWilliam H Frey
Jan 13, 2006·Biochemical Pharmacology·Nieves MárquezEduardo Muñoz
Jun 6, 2015·Organic Letters·Joshua SchwochertR Scott Lokey
Jul 21, 2009·Chemistry & Biology·Marisol MontolioEduardo Soriano
Apr 12, 2007·Biopolymers·Justin K Murray, Samuel H Gellman
Jan 13, 2005·The Journal of Pharmacology and Experimental Therapeutics·Maria J Abad-MerinAntonio Ferrer-Montiel
May 27, 2015·Chembiochem : a European Journal of Chemical Biology·Glòria Vendrell-NavarroHerbert Waldmann
Oct 8, 2003·CNS Drug Reviews·Ana M Sánchez-PérezVicente Felipo

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