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Targeting metabotropic glutamate receptors for novel treatments of schizophrenia

Overview of attention for article published in Molecular Brain, April 2017
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  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Average Attention Score compared to outputs of the same age and source

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4 X users
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1 Wikipedia page

Citations

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108 Dimensions

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207 Mendeley
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Title
Targeting metabotropic glutamate receptors for novel treatments of schizophrenia
Published in
Molecular Brain, April 2017
DOI 10.1186/s13041-017-0293-z
Pubmed ID
Authors

James Maksymetz, Sean P. Moran, P. Jeffrey Conn

Abstract

Support for the N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia has led to increasing focus on restoring proper glutamatergic signaling as an approach for treatment of this devastating disease. The ability of metabotropic glutamate (mGlu) receptors to modulate glutamatergic neurotransmission has thus attracted considerable attention for the development of novel antipsychotics. Consisting of eight subtypes classified into three groups based on sequence homology, signal transduction, and pharmacology, the mGlu receptors provide a wide range of targets to modulate NMDAR function as well as glutamate release. Recently, allosteric modulators of mGlu receptors have been developed that allow unprecedented selectivity among subtypes, not just groups, facilitating the investigation of the effects of subtype-specific modulation. In preclinical animal models, positive allosteric modulators (PAMs) of the group I mGlu receptor mGlu5 have efficacy across all three symptom domains of schizophrenia (positive, negative, and cognitive). The discovery and development of mGlu5 PAMs that display unique signal bias suggests that efficacy can be retained while avoiding the neurotoxic effects of earlier compounds. Interestingly, mGlu1 negative allosteric modulators (NAMs) appear efficacious in positive symptom models of the disease but are still in early preclinical development. While selective group II mGlu receptor (mGlu2/3) agonists have reached clinical trials but were unsuccessful, specific mGlu2 or mGlu3 receptor targeting still hold great promise. Genetic studies implicated mGlu2 in the antipsychotic effects of group II agonists and mGlu2 PAMs have since entered into clinical trials. Additionally, mGlu3 appears to play an important role in cognition, may confer neuroprotective effects, and thus is a promising target to alleviate cognitive deficits in schizophrenia. Although group III mGlu receptors (mGlu4/6/7/8) have attracted less attention, mGlu4 agonists and PAMs appear to have efficacy across all three symptoms domains in preclinical models. The recent discovery of heterodimers comprising mGlu2 and mGlu4 may explain the efficacy of mGlu4 selective compounds but this remains to be determined. Taken together, compounds targeting mGlu receptors, specifically subtype-selective allosteric modulators, provide a compelling alternative approach to fill the unmet clinical needs for patients with schizophrenia.

X Demographics

X Demographics

The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 207 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 207 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 35 17%
Student > Bachelor 33 16%
Researcher 28 14%
Student > Ph. D. Student 19 9%
Student > Doctoral Student 11 5%
Other 22 11%
Unknown 59 29%
Readers by discipline Count As %
Neuroscience 34 16%
Biochemistry, Genetics and Molecular Biology 25 12%
Pharmacology, Toxicology and Pharmaceutical Science 25 12%
Medicine and Dentistry 21 10%
Psychology 11 5%
Other 27 13%
Unknown 64 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 October 2019.
All research outputs
#6,200,950
of 22,968,808 outputs
Outputs from Molecular Brain
#290
of 1,117 outputs
Outputs of similar age
#98,265
of 309,828 outputs
Outputs of similar age from Molecular Brain
#6
of 11 outputs
Altmetric has tracked 22,968,808 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,117 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has gotten more attention than average, scoring higher than 73% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 309,828 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.