European Journal of Pharmacology: Molecular Pharmacology
Short communicationThe neuroprotective properties of ifenprodil, a novel NMDA receptor antagonist, in neuronal cell culture toxicity studies
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The Good and Bad Sides of NAAG
2016, Advances in PharmacologyCitation Excerpt :The side effects such as psychotomimetic effects, memory impairment, and neurotoxicity, which are usually exerted by NMDA receptor channel blockers and competitive antagonists, are not seen when drugs targeting specific subunits, such as ifenprodil, are used as neuroprotective agents. These reduced side effects may be ascribed to the GluN2B subunit specificity mediated by ifenprodil and related compounds (Baskaya et al., 1997; Geng et al., 1997; Gotti et al., 1988; Graham et al., 1992; Liu et al., 2007; McDonald & Johnston, 1990; Picconi et al., 2006; Shalaby et al., 1992; Tamura et al., 1993; Yamakura & Shimoji, 1999). Interestingly, both NAAG and 2-PMPA show robust neuroprotection without side effects when tested in stroke models, similar to other GluN2B-specific therapies (Cai et al., 2002; Lu et al., 2000; Slusher et al., 1999; Tortella et al., 2000).
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
2014, Progress in NeurobiologyCitation Excerpt :Consistent with this finding, the differential roles of synaptic and extrasynaptic NMDARs in neuronal death and survival can also be partially explained by the presence of distinct NMDAR subunits in these sub-cellular locations (Fig. 1A and B). Selective GluN2BR antagonists are highly neuroprotective in models of cerebral ischemia and other neurodegenerative diseases (Chen et al., 2008; DeRidder et al., 2006; Gotti et al., 1988; Graham et al., 1992; Liu et al., 2007; O’Donnell et al., 2006; von Engelhardt et al., 2007; Zhou and Baudry, 2006), whereas selective GluN2AR antagonists are poorly neuroprotective and in several studies, exacerbated neuronal death (Chen et al., 2008; DeRidder et al., 2006; Liu et al., 2007). Importantly, in the adult rat forebrain, the GluN2AR and GluN2BR NMDAR subtypes can confer neuronal survival and neuronal death, respectively, independently of their subcellular location.
The Subtype of GluN2 C-terminal Domain Determines the Response to Excitotoxic Insults
2012, NeuronCitation Excerpt :This compositional diversity raises the (unresolved) question as to whether the GluN2 subtype (GluN2A versus GluN2B) differentially influences the toxicity of Ca2+ influx through NMDARs. There is evidence that GluN2B- and GluN2A-containing NMDARs are both capable of mediating excitotoxicity (Graham et al., 1992; Lau and Tymianski, 2010; von Engelhardt et al., 2007); however, whether they do so with differing efficiency or mechanisms is unclear. In answering questions relating to subunit-specific function (including excitotoxicity), it is becoming clear that pharmacological approaches are of limited use, given the tools currently available (Neyton and Paoletti, 2006).
Delayed mitochondrial membrane potential disruption by ATP in cultured rat hippocampal neurons exposed to N-methyl-D-aspartate
2012, Journal of Pharmacological Sciences