title: From bench to bedside: mGluR2 positive allosteric modulators as medications to treat substance use disorders.
abstract: This paper provides an overview of the role of type 2 metabotropic glutamate receptors (mGluR2) in addiction and behaviors reflecting addictive processes.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division 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.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Acri
authors.affiliation: AstraZeneca Neuroscience Innovative Medicines and Early Development Biotech Unit, 141 Portland Street, Cambridge, MA, 02139, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Cross
authors.affiliation: Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, 6001 Executive Blvd, Suite 4123, MSC 9551, Bethesda, MD, 20892-9551, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Skolnick
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage; D010069:Oxadiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012646:Self Administration / Q000379:methods; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism*; D061485:Tobacco Use Cessation Devices; D016896:Treatment Outcome
chemical_list: C000608263:AZD8529; D007211:Indoles; D010069:Oxadiazoles; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D009538:Nicotine
keywords: Animal models; Athina Markou; Cocaine; Cue-induced reinstatement; Glutamate; Nicotine; Self-administration; Smoking cessation; mGluR2