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Updated: Mar 9, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
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Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission

Published on: August 16, 2018

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From bench to bedside: mGluR2 positive allosteric modulators as medications to treat substance use disorders

Jane B Acri1, Alan J Cross2, Phil Skolnick3

  • 1Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, 6001 Executive Blvd, Suite 4123, MSC 9551, Bethesda, MD, 20892-9551, USA. jacri@nih.gov.

Psychopharmacology
|December 21, 2016
PubMed
Abstract

Insights

Type 2 metabotropic glutamate receptors (mGluR2) are implicated in addiction. An mGluR2 positive allosteric modulator (AZD8529) showed promise in preclinical models for smoking cessation, despite a negative schizophrenia trial.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Type 2 metabotropic glutamate receptors (mGluR2) play a role in addiction.
  • Understanding the role of mGluR2 in addictive behaviors is crucial for developing novel therapeutics.

Purpose of the Study:

  • To provide an overview of the role of mGluR2 in addiction.
  • To discuss the development and clinical trial of AZD8529, an mGluR2 positive allosteric modulator (PAM).

Main Methods:

  • Review of preclinical studies demonstrating the role of mGluR2 in addiction models.
  • Description of the preclinical efficacy of AZD8529 in attenuating nicotine self-administration and cue-induced reinstatement.
  • Overview of a Phase II clinical trial for smoking cessation.

Main Results:

  • AZD8529, an mGluR2 PAM, attenuated nicotine self-administration and cue-induced reinstatement in preclinical models.
  • AZD8529 did not separate from placebo in a Phase II schizophrenia trial.

Conclusions:

  • Preclinical findings supported the investigation of AZD8529 for smoking cessation.
  • Innovative features of the Phase II clinical trial are highlighted, with results anticipated.
Keywords:
Animal modelsAthina MarkouCocaineCue-induced reinstatementGlutamateNicotineSelf-administrationSmoking cessationmGluR2

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