The mGlu5 receptor negative allosteric modulator mavoglurant reduces escalated cocaine self-administration in male and female rats.

Rationale: Cocaine use disorder (CUD) is a brain disorder for which there is no Food and Drug Administration-approved pharmacological treatment. Evidence suggests that glutamate and metabotropic glutamate receptor subtype 5 (mGlu5) play critical roles in synaptic plasticity, neuronal development, and psychiatric disorders.

Objective: In the present study, we tested the hypothesis that the mGlu5 receptor is functionally involved in intravenous cocaine self-administration and assessed the effects of sex and cocaine exposure history.

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

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.

Considerations in the Evaluation of Potential Efficacy of Medications for Alcohol and Drug Use Disorders: An Editorial.

The societal burden created by alcohol and drug use disorders is estimated to be on the order of hundreds of billions of dollars, creating a need for effective medications to reduce use and prevent relapse. While there are FDA-approved medications to facilitate abstinence and prevent relapse for some indications including, alcohol, tobacco, and opiate use disorders, there are no approved treatments for other abused substances, including cocaine, methamphetamine, and cannabis, leaving these critical medical needs unmet. The development of such medications has fallen largely to the government with efforts spearheaded by the National Institute on Drug Abuse and the National Institute on Alcoholism and Alcohol Abuse.

Dopamine D3 Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs.

The chronic and relapsing nature of addiction presents unique challenges for ensuring the safety of a potential medication. A patient may use cocaine, for example, while taking the medication or take more medication than prescribed. Thus, a potential medication must be safe and not exacerbate the effects of cocaine.