2021
DOI: 10.3389/fnins.2021.700822
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Partial mGlu5 Negative Allosteric Modulator M-5MPEP Demonstrates Antidepressant-Like Effects on Sleep Without Affecting Cognition or Quantitative EEG

Abstract: Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor subtype 5 (mGlu5) demonstrate anxiolytic-like and antidepressant-like effects yet concern regarding adverse effect liability remains. Functional coupling of mGlu5 with ionotropic N-methyl-D-aspartate receptors (NMDARs) represents a potential mechanism through which full inhibition leads to adverse effects, as NMDAR inhibition can induce cognitive impairments and psychotomimetic-like effects. Recent development of “par… Show more

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Cited by 8 publications
(10 citation statements)
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“…Aberrant elevations in resting-state gamma power have been identified in patients with schizophrenia and correspond to positive symptoms and cognitive impairment [ 22 , 23 , 24 , 25 ]. Importantly, gamma power is directly impacted by changes in NMDA receptor function, and NMDA receptor antagonists including MK-801 increase gamma power and disrupt cognition [ 30 , 34 ]. Although sex- and age-related differences are relevant factors influencing the pathophysiology of schizophrenia, how these variables affect NMDA receptor function has been largely overlooked in preclinical studies as well as in clinical trials [ 35 ].…”
Section: Discussionmentioning
confidence: 99%
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“…Aberrant elevations in resting-state gamma power have been identified in patients with schizophrenia and correspond to positive symptoms and cognitive impairment [ 22 , 23 , 24 , 25 ]. Importantly, gamma power is directly impacted by changes in NMDA receptor function, and NMDA receptor antagonists including MK-801 increase gamma power and disrupt cognition [ 30 , 34 ]. Although sex- and age-related differences are relevant factors influencing the pathophysiology of schizophrenia, how these variables affect NMDA receptor function has been largely overlooked in preclinical studies as well as in clinical trials [ 35 ].…”
Section: Discussionmentioning
confidence: 99%
“…Rats were anesthetized with isoflurane (3–5% induction, 1–3% maintenance) and implanted with a subcutaneous transmitter (HD-S02; Data Sciences International [DSI], Minneapolis, MN, USA) as previously described [ 34 , 85 ]. In brief, transmitters were implanted subcutaneously near the dorsal flank, and four wires were tunneled towards the skull.…”
Section: Methodsmentioning
confidence: 99%
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“…Both the slow and delta oscillations arise from variations in the resting membrane potentials of both thalamic and cortical neurons [ 74 , 75 ]. These reciprocally interconnected cells can switch between depolarized, the so called ‘UP’ state, and hyperpolarized, the ‘DOWN’ state.…”
Section: The Regulation Of Sleep States By Mglu5 Receptorsmentioning
confidence: 99%
“…In the last decade, there have been enormous efforts in developing specific mGlu5 receptor allosteric modulators, positive and negative allosteric modulators (PAMs and NAMs), which bind to sites found in the 7-TM domain of the receptor. Allosteric ligands of the mGlu5 receptor remain an attractive therapeutic strategy for different neurological and psychiatric disorders and comorbid sleep disturbances [ 75 ].…”
Section: The Regulation Of Sleep States By Mglu5 Receptorsmentioning
confidence: 99%