Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators DOI Creative Commons
Janko Kos, Monica Langiu, Shane D. Hellyer

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(12), P. 3671 - 3690

Published: Nov. 5, 2024

Metabotropic glutamate receptors are a family of eight class C G protein-coupled regulating higher order brain functions including cognition and motion. have thus been heavily investigated as potential drug targets for treating neurological disorders. Drug discovery efforts directed toward metabotropic receptor subtype 5 (mGlu5) particularly fruitful, with wealth candidates pharmacological tools identified. mGlu5 negative allosteric modulators (NAMs) promising novel therapeutics developmental, neuropsychiatric neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's Parkinson's amyotrophic lateral sclerosis, autism spectrum disorders, substance use stroke, anxiety depression) show promise in ameliorating adverse effects induced by other medications L-dopa dyskinesia Disease). However, despite preclinical success, NAMs yet to reach the market due poor safety efficacy profiles clinical trials. Herein, we review physiology signal transduction mGlu5. We provide comprehensive critique therapeutic options respect inhibitors, spanning from orthosteric antagonists NAMs. Finally, address challenges associated development highlight future directions guide rational safe effective therapeutics.

Language: Английский

A type-5 metabotropic glutamate receptor-perineuronal net axis shapes the function of cortical GABAergic interneurons in chronic pain DOI Creative Commons
Giada Mascio, Ferdinando Nicoletti, Giuseppe Battaglia

et al.

Journal of Anesthesia Analgesia and Critical Care, Journal Year: 2025, Volume and Issue: 5(1)

Published: Feb. 21, 2025

Language: Английский

Citations

0
Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators DOI Creative Commons
Janko Kos, Monica Langiu, Shane D. Hellyer

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(12), P. 3671 - 3690

Published: Nov. 5, 2024

Metabotropic glutamate receptors are a family of eight class C G protein-coupled regulating higher order brain functions including cognition and motion. have thus been heavily investigated as potential drug targets for treating neurological disorders. Drug discovery efforts directed toward metabotropic receptor subtype 5 (mGlu5) particularly fruitful, with wealth candidates pharmacological tools identified. mGlu5 negative allosteric modulators (NAMs) promising novel therapeutics developmental, neuropsychiatric neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's Parkinson's amyotrophic lateral sclerosis, autism spectrum disorders, substance use stroke, anxiety depression) show promise in ameliorating adverse effects induced by other medications L-dopa dyskinesia Disease). However, despite preclinical success, NAMs yet to reach the market due poor safety efficacy profiles clinical trials. Herein, we review physiology signal transduction mGlu5. We provide comprehensive critique therapeutic options respect inhibitors, spanning from orthosteric antagonists NAMs. Finally, address challenges associated development highlight future directions guide rational safe effective therapeutics.

Language: Английский

Citations

0