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

Abstract

Objective

This paper provides an overview of the role of type 2 metabotropic glutamate receptors (mGluR2) in addiction and behaviors reflecting addictive processes.

Results

AZD8529, an mGluR2 positive allosteric modulator (PAM), failed to separate from placebo in a phase II schizophrenia trial. The demonstration by Athina Markou’s laboratory that AZD8529 attenuated both nicotine self-administration and cue-induced reinstatement was a key factor in the decision to move this compound into a smoking cessation study.

Conclusion

Here, we highlight Markou laboratory’s contribution to this project, as well as several innovative features of the phase II clinical trial that has already completed enrollment with top line results expected in early 2017.

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Correspondence to Jane B. Acri.

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JBA and PS are employees of the US Government and have no conflicts of interest. AJC is an employee of AstraZeneca.

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Acri, J.B., Cross, A.J. & Skolnick, P. From bench to bedside: mGluR2 positive allosteric modulators as medications to treat substance use disorders. Psychopharmacology 234, 1347–1355 (2017). https://doi.org/10.1007/s00213-016-4501-9

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Keywords

  • Athina Markou
  • mGluR2
  • Cocaine
  • Nicotine
  • Glutamate
  • Self-administration
  • Cue-induced reinstatement
  • Animal models
  • Smoking cessation