Journal ArticleDOI
The mGlu5 positive allosteric modulator LSN2463359 differentially modulates motor, instrumental and cognitive effects of NMDA receptor antagonists in the rat
TLDR
The results indicate that the interactions between mGlu₅ and NMDA receptors are dependent on both the mechanism of the blockade of the receptor and the behavioural domain under investigation, which has implications for the preclinical use of NMDA receptor antagonists in the prediction of potential therapeutic efficacy.About:
This article is published in Neuropharmacology.The article was published on 2013-01-01. It has received 41 citations till now. The article focuses on the topics: Phencyclidine & CDPPB.read more
Citations
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Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders
TL;DR: An increased understanding is developed of the major advantages and broad range of activities that can be achieved with new allosteric modulators of G protein-coupled receptors through selective modulation of specific signalling pathways, differential effects on GPCR homodimer versus heterodimers, and other properties.
Journal ArticleDOI
Development of allosteric modulators of GPCRs for treatment of CNS disorders
TL;DR: The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction.
Journal ArticleDOI
Biased mGlu5-positive allosteric modulators provide in vivo efficacy without potentiating mGlu5 modulation of NMDAR currents
Jerri M. Rook,Zixiu Xiang,Xiaohui Lv,Ayan Ghoshal,Jonathan W. Dickerson,Thomas M. Bridges,Kari A. Johnson,Daniel J. Foster,Karen J. Gregory,Karen J. Gregory,Paige N. Vinson,Analisa D. Thompson,Nellie Byun,Rebekah L. Collier,Michael Bubser,Michael T. Nedelcovych,Robert W. Gould,Shaun R. Stauffer,J. Scott Daniels,Colleen M. Niswender,Hilde Lavreysen,Claire Mackie,Susana Conde-Ceide,Jesús Alcázar,José Manuel Bartolomé-Nebreda,Gregor James Macdonald,John Talpos,Thomas Steckler,Carrie K. Jones,Craig W. Lindsley,P. Jeffrey Conn +30 more
TL;DR: Interestingly, VU0409551 produced robust antipsychotic-like and cognition-enhancing activity in animal models and suggest that modulation of NMDAR currents is not critical for in-vivo efficacy, providing surprising new mechanistic insights into the actions of mGlu5 PAMs.
Journal ArticleDOI
Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors.
TL;DR: The review covers the evolution of research in this field over the last 25 years and proposes assigning drugs to 18 categories according to their mechanism(s) of action.
Journal ArticleDOI
Metabotropic glutamate receptor 5 in the pathology and treatment of schizophrenia
Natalie Matosin,Kelly A. Newell +1 more
TL;DR: The molecular, animal and human data to support and refute the involvement of mGluR5 in the pathology of schizophrenia will be explored, as well as aspects of m GluR 5 that require further characterisation.
References
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Journal ArticleDOI
Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses.
John H. Krystal,Laurence P. Karper,John Seibyl,Glenna K. Freeman,Richard C. Delaney,J. Douglas Bremner,George R. Heninger,Malcolm B. Bowers,Dennis S. Charney +8 more
TL;DR: These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.
Journal ArticleDOI
Recent advances in the phencyclidine model of schizophrenia.
TL;DR: It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP and the findings suggest that endogenous dysfunction of NMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia.
Journal ArticleDOI
Glutamate receptor dysfunction and schizophrenia.
John W. Olney,Nuri B. Farber +1 more
TL;DR: It is proposed that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents, a better understanding of this mechanism may lead to improved pharmacotherapy in schizophrenia.
Journal ArticleDOI
Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat
TL;DR: It is concluded that medial frontal cortex of the rat has functional similarity to primate lateral prefrontal cortex, shown to mediate shifts in attention between perceptual dimensions of complex stimuli.
Journal ArticleDOI
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate
TL;DR: The results suggest that reduction of synaptic excitation mediated via NMA receptors contributes to the anaesthetic/analgesic properties of these two dissociative anaesthetics.
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