Comments on “Memantine Blocks α7* Nicotinic Acetylcholine Receptors More Potently Than N-Methyl-d-aspartate Receptors in Rat Hippocampal Neurons”

Banerjee, Pradeep; Samoriski, Gary M.; Gupta, Sandeep

doi:10.1124/jpet.104.081976

Cited by 56 publications

(18 citation statements)

References 17 publications

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“…Moreover, the other class of drugs approved for the treatment of AD represented by memantine, a use-dependent calcium channel blocker of the glutamate NMDA receptor, was recently shown to more potently block α7nAChRs than NMDA receptors in rat hippocampal neurons (Aracava et al, 2005; Banerjee et al, 2005), providing some extra evidence supporting the potential beneficial effect of antagonizing α7nAChRs.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the 7 Nicotinic Acetylcholine Receptor Gene Improves Cognitive Deficits and Synaptic Pathology in a Mouse Model of Alzheimer's Disease

Dziewczapolski¹,

Glogowski²,

Masliah³

et al. 2009

Journal of Neuroscience

181

147

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It has been recently shown that the Alzheimer's disease (AD) pathogenic peptide amyloid ␤ 1-42 (A␤ 1-42 ) binds to the ␣7 nicotinic acetylcholine receptor (␣7nAChR) with high affinity and the ␣7nAChR and A␤ 1-42 are both found colocalized in neuritic plaques of human brains with AD. Moreover, the intraneuronal accumulation of A␤ 1-42 was shown to be facilitated by its high-affinity binding to the ␣7nAChR, and ␣7nAChR activation mediates A␤-induced tau protein phosphorylation. To test the hypothesis that ␣7nAChRs are involved in AD pathogenesis, we used a transgenic mouse model of AD overexpressing a mutated form of the human amyloid precursor protein (APP) and lacking the ␣7nAChR gene (APP␣7KO). We have shown that, despite the presence of high amounts of APP and amyloid deposits, deleting the ␣7nAChR subunit in the mouse model of AD leads to a protection from the dysfunction in synaptic integrity (pathology and plasticity) and learning and memory behavior. Specifically, APP␣7KO mice express APP and A␤ at levels similar to APP mice, and yet they were able to solve a cognitive challenge such as the Morris water maze test significantly better than APP, with performances comparable to control groups. Moreover, deleting the ␣7nAChR subunit protected the brain from loss of the synaptic markers synaptophysin and MAP2, reduced the gliosis, and preserved the capacity to elicit long-term potentiation otherwise deficient in APP mice. These results are consistent with the hypothesis that the ␣7nAChR plays a role in AD and suggest that interrupting ␣7nAChR function could be beneficial in the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Deletion of the 7 Nicotinic Acetylcholine Receptor Gene Improves Cognitive Deficits and Synaptic Pathology in a Mouse Model of Alzheimer's Disease

Dziewczapolski¹,

Glogowski²,

Masliah³

et al. 2009

Journal of Neuroscience

181

147

View full text Add to dashboard Cite

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“…Beside the action on NMDA receptors, memantine was proved to be a α7 nAChR antagonist with median inhibitory concentration 0.34 μM [80]. Although Aracava et al considered antagonism of memantine on α7 nAChR as a negative phenomenon in Alzheimer’s disease treatment [80], the antagonism is considered to be beneficial in Alzheimer’s disease treatment according to other scientists [81]. However, the significance of the antagonism should be elucidated and antagonism suitability for Alzheimer’s disease treatment is not a common view; more trials are needed [82].…”

Section: Antagonists Of α7 Nachrmentioning

confidence: 99%

Alpha7 Nicotinic Acetylcholine Receptor Is a Target in Pharmacology and Toxicology

Pohanka

2012

IJMS

153

106

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Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an important part of the cholinergic nerve system in the brain. Moreover, it is associated with a cholinergic anti-inflammatory pathway in the termination of the parasympathetic nervous system. Antagonists of α7 nAChR are a wide group represented by conotoxin and bungarotoxin. Even Alzheimer’s disease drug memantine acting as an antagonist in its side pathway belongs in this group. Agonists of α7 nAChR are suitable for treatment of multiple cognitive dysfunctions such as Alzheimer’s disease or schizophrenia. Inflammation or even sepsis can be ameliorated by the agonistic acting compounds. Preparations RG3487, SEN34625/WYE-103914, SEN12333, ABT-107, Clozapine, GTS-21, CNI-1493, and AR-R17779 are representative examples of the novel compounds with affinity toward the α7 nAChR. Pharmacological, toxicological, and medicinal significance of α7 nAChR are discussed throughout this paper.

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“…It is important to note though, that there has been some debate regarding the selectivity of compounds used in preclinical studies, where it has been suggested that some actions of the NMDAantagonists may have been mediated by nicotinic receptors (Glick et al, 2001;Zakharova et al, 2005). In addition, the possibility that high doses of memantine may have actions at nicotinic-receptors has been discussed in the clinical literature (Maskell et al 2003;Banerjee et al, 2005). As a control therefore, for any possible actions of memantine at acetylcholine receptors we compared its effects with the nicotinic-receptor antagonist mecamylamine.…”

Section: Introductionmentioning

confidence: 99%

Differential Involvement of Glutamatergic Mechanisms in the Cognitive and Subjective Effects of Smoking

Jackson

Nešić

Groombridge

et al. 2008

Neuropsychopharmacol

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There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior. Keywords: smoking; memantine; mecamylamine; subjective; craving; cognition INTRODUCTIONNicotine is known to have positively reinforcing, subjective and cognitive effects (Stolerman and Jarvis, 1995;Levin et al, 2006). In humans, some of the measurable subjective effects of nicotine include 'buzzed', 'dizzy', 'stimulated' (Perkins et al, 1999) while positive cognitive effects include improvements in attention (Wesnes and Warburton, 1984) and memory (Rusted et al, 1998). The neurobiological mechanisms underlying these actions of nicotine are complex, involving not only a direct action of nicotine at receptors for acetylcholine, but also changes in release of other neurotransmitters, such as dopamine and glutamate (Watkins et al, 2000).Neurochemical studies have demonstrated that, at concentrations achieved during smoking, nicotine can enhance the release and function of glutamate, through an action at presynaptic receptors (eg McGehee et al, 1995). Such studies have determined that nicotine can alter glutamate release in several different areas of the brain, including the ventral tegmental area (Schilstrom et al, 1998(Schilstrom et al, , 2000Fu et al, 2000;Mansvelder and McGehee, 2000) the nucleus accumbens (Fu et al, 2000;Reid et al, 2000) the pre-frontal cortex (Toth et al, 1993;Vidal, 1994;Gioanni et al, 1999;) and the hippocampus (Gray et al, 1996;Radcliffe et al, 1999). These are areas thought to be involved in mediating the subjective (Rosecrans and Meltzer, 1981;Shoaib and Stolerman, 1992;Miyata et al, 1999) rewarding (Corrigall et al, 1994;Stolerman, 1996;Schroeder et al, 2001) and cognitive actions of nicotine (Stolerman, 1996;Levin et al, 1999).There is also growing evidence from behavioral models to indicate a role for glutamate in neurobiological mechanisms underlying the actions of nicotine....

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Comments on “Memantine Blocks α7* Nicotinic Acetylcholine Receptors More Potently Than N-Methyl-d-aspartate Receptors in Rat Hippocampal Neurons”

Cited by 56 publications

References 17 publications

Deletion of the 7 Nicotinic Acetylcholine Receptor Gene Improves Cognitive Deficits and Synaptic Pathology in a Mouse Model of Alzheimer's Disease

Deletion of the 7 Nicotinic Acetylcholine Receptor Gene Improves Cognitive Deficits and Synaptic Pathology in a Mouse Model of Alzheimer's Disease

Alpha7 Nicotinic Acetylcholine Receptor Is a Target in Pharmacology and Toxicology

Differential Involvement of Glutamatergic Mechanisms in the Cognitive and Subjective Effects of Smoking

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