Neuropharmacological Insight from Allosteric Modulation of mGlu Receptors.

Abstract:

:The metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors (GPCRs) that regulate cell physiology throughout the nervous system. The potential of mGlu receptors as therapeutic targets has been bolstered by current research that has provided insight into the diverse modes of mGlu activation and signaling. In particular, the allosteric modulation of mGlu receptors represents a major area of focus in studies of basic pharmacology as well as drug development, largely due to the high subtype specificity achievable by targeting allosteric sites on mGlu receptors. These provide sophisticated regulation of neuronal excitability and synaptic transmission to influence behavioral output. Here, we review how these allosteric mechanisms have been leveraged preclinically to demonstrate the therapeutic potential of allosteric modulators for neurological and neuropsychiatric disorders, such as autism, cognitive impairment, Parkinson's disease (PD), stress, and schizophrenia.

journal_name

Trends Pharmacol Sci

authors

Stansley BJ,Conn PJ

doi

10.1016/j.tips.2019.02.006

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

240-252

issue

4

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(19)30037-9

journal_volume

40

pub_type

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