Partial mGlu₅ Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Robert W GouldCarrie K Jones

Abstract

Cocaine abuse remains a public health concern for which pharmacotherapies are largely ineffective. Comorbidities between cocaine abuse, depression, and anxiety support the development of novel treatments targeting multiple symptom clusters. Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor 5 (mGlu5) subtype are currently in clinical trials for the treatment of multiple neuropsychiatric disorders and have shown promise in preclinical models of substance abuse. However, complete blockade or inverse agonist activity by some full mGlu5 NAM chemotypes demonstrated adverse effects, including psychosis in humans and psychotomimetic-like effects in animals, suggesting a narrow therapeutic window. Development of partial mGlu5 NAMs, characterized by their submaximal but saturable levels of blockade, may represent a novel approach to broaden the therapeutic window. To understand potential therapeutic vs adverse effects in preclinical behavioral assays, we examined the partial mGlu5 NAMs, M-5MPEP and Br-5MPEPy, in comparison with the full mGlu5 NAM MTEP across models of addiction and psychotomimetic-like activity. M-5MPEP, Br-5MPEPy, and MTEP dose-dependently decreased cocaine self-administration...Continue Reading

References

Aug 31, 2002·Psychopharmacology·Franco BorsiniDonatella Marazziti
Mar 28, 2003·The Journal of Pharmacology and Experimental Therapeutics·Gene G KinneyP Jeffrey Conn
May 29, 2003·Current Drug Targets. CNS and Neurological Disorders·M J Marino, P Jeffrey Conn
Dec 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Cyril GoudetJean Philippe Pin
Mar 11, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Houman HomayounBita Moghaddam
Aug 12, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Chris S BusseNicholas D P Cosford
Nov 24, 2004·Biological Psychiatry·Nora D Volkow
Mar 16, 2005·Behavioural Pharmacology·A GraviusW Danysz
Aug 27, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Pia Bäckström, Petri Hyytiä
Oct 5, 2007·Current Psychiatry Reports·Kathleen T BradyBryan K Tolliver
Oct 10, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carrie K JonesP Jeffrey Conn
Jan 1, 2009·Nature Reviews. Drug Discovery·P Jeffrey ConnCraig W Lindsley
Nov 7, 2009·Trends in Pharmacological Sciences·Michael K Bird, Andrew J Lawrence
Nov 7, 2009·The Journal of Pharmacology and Experimental Therapeutics·Takato HiranitaJonathan L Katz
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Colleen M Niswender, P Jeffrey Conn
Jul 24, 2010·Neuroscience Bulletin·Hua-Cheng YanTian-Ming Gao
Apr 13, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Daniela BergBaltazar Gomez-Mancilla
Aug 6, 2011·The International Journal of Neuropsychopharmacology·Robyn M BrownAndrew J Lawrence
Aug 28, 2012·ACS Medicinal Chemistry Letters·Thomas M KeckAmy Hauck Newman
Sep 19, 2012·Schizophrenia Bulletin·Joseph T Coyle

❮ Previous
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Citations

Jul 14, 2016·Expert Opinion on Drug Discovery·Agnieszka Pałucha-Poniewiera, Andrzej Pilc
Nov 17, 2016·Psychopharmacology·Cristiano ChiamuleraDavid J K Balfour
Dec 15, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Katie Leach, Karen J Gregory
Jan 23, 2017·European Journal of Medicinal Chemistry·Xavier Gómez-SantacanaAmadeu Llebaria
Jan 10, 2017·Expert Opinion on Therapeutic Patents·Kyle A Emmitte
Nov 6, 2018·Clinical Science·Phuc N H TrinhKaren J Gregory
Jan 11, 2018·Translational Psychiatry·Funda AkkusGregor Hasler
Oct 17, 2016·The International Journal of Neuropsychopharmacology·Hanne Mette HoffmannMichel Vignes
Apr 3, 2019·Chronic Stress·Shigeyuki ChakiKenichi Fukumoto
Aug 2, 2019·Brain Sciences·Chelsea R KastenTiffany A Wills
Dec 29, 2020·Pharmacology & Therapeutics·Ewa Niedzielska-AndresEdmund Przegaliński
Mar 12, 2021·Pharmacology & Therapeutics·Johannes PetzoldEdythe D London
Jun 6, 2021·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Li-Da SuYing Shen
Feb 6, 2019·Journal of Medicinal Chemistry·Quinn CoughlinDario Doller

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