ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Partial mGlu₅ Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- (R)-ketamine induces mGluPsychopharmacology · 2025Article
- Depression-like effects induced by chronic unpredictable mild stress in mice are rapidly reversed by a partial negative allosteric modulator of mGluPsychopharmacology · 2025Article
- [Pharmacological reports : PR · 2025Article
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- The mGlu5 receptor negative allosteric modulator mavoglurant reduces escalated cocaine self-administration in male and female rats.Psychopharmacology · 2024Article
- Partial mGluPharmacological reports : PR · 2024Article
- Metabotropic glutamate receptor function and regulation of sleep-wake cycles.International review of neurobiology · 2023Article
- Group 1 Metabotropic Glutamate Receptors in Neurological and Psychiatric Diseases: Mechanisms and Prospective.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- Targeting metabotropic glutamate receptors for the treatment of depression and other stress-related disorders.Neuropharmacology · 2021Review
- Partial mGluFrontiers in neuroscience · 2021Article
- Acute Negative Allosteric Modulation of MACS chemical neuroscience · 2019Article
- Metabotropic Glutamate Receptor Subtype 5 in Alcohol-Induced Negative Affect.Brain sciences · 2019Review
- Kinetic and system bias as drivers of metabotropic glutamate receptor 5 allosteric modulator pharmacology.Neuropharmacology · 2019Article
- Selective inhibition of MAddiction biology · 2018Article
- Metabotropic glutamate receptor 5 binding in male patients with alcohol use disorder.Translational psychiatry · 2018Article
- Review
- Metabotropic glutamate receptor 5 as a potential target for smoking cessation.Psychopharmacology · 2017Review
- Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration.The international journal of neuropsychopharmacology · 2017Article
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
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 and attenuated the discriminative stimulus effects of cocaine. M-5MPEP and Br-5MPEPy also demonstrated antidepressant- and anxiolytic-like activity. Dose-dependent effects of partial and full mGlu5 NAMs in these assays corresponded with increasing in vivo mGlu5 occupancy, demonstrating an orderly occupancy-to-efficacy relationship. PCP-induced hyperlocomotion was potentiated by MTEP, but not by M-5MPEP and Br-5MPEPy. Further, MTEP, but not M-5MPEP, potentiated the discriminative-stimulus effects of PCP. The present data suggest that partial mGlu5 NAM activity is sufficient to produce therapeutic effects similar to full mGlu5 NAMs, but with a broader therapeutic index.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.