Related Experiment Video
Updated: Sep 30, 2026
Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements
Published on: January 7, 2019
Anxiolytic-like activity of the mGluR5 antagonist MPEP: a comparison with diazepam and buspirone
Jesse Brodkin1, Chris Busse, Stacey J Sukoff
1Merck Research Laboratories, MRLSD-B1, 3535 General Atomics Court, San Diego, CA 92121, USA. Jesse_Brodkin@Merck.com
Abstract:
The selective and systemically active antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)pyridine (MPEP) was shown to display anxiolytic-like activity in a number of unconditioned assays of stress and anxiety (elevated plus maze, shock probe burying, marble burying, social interaction, and stress-induced hyperthermia) in rodents. In this report, we extend these observations found using unconditioned models of anxiety to include three models of conditioned anxiety, comparing the activity of MPEP to the clinically used anxiolytics, diazepam, and buspirone. MPEP and diazepam, but not buspirone, showed anxiolytic-like activity in the fear-potentiated startle (FPS) model. In a conditioned ultrasonic vocalization (USV) procedure, MPEP, diazepam, and buspirone reduced vocalizations to a similar degree. In the modified Geller-Seifter procedure, MPEP, diazepam, and buspirone displayed statistically significant anxiolytic-like activity, increasing the number of punished responses. Thus, these findings confirm and extend previous reports that MPEP exhibits anxiolytic-like activity in rats, and suggests that development of mGluR5 antagonists may provide a novel approach to treating anxiety disorders.
Insights
The metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP demonstrates anxiolytic-like effects in conditioned anxiety models. These findings suggest mGluR5 antagonists could be a novel treatment for anxiety disorders.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Metabotropic glutamate receptor subtype 5 (mGluR5) antagonists, like MPEP, show anxiolytic-like activity in unconditioned rodent models.
- Anxiety disorders are a significant public health concern, necessitating novel therapeutic targets.
Purpose of the Study:
- To evaluate the anxiolytic-like efficacy of MPEP in conditioned anxiety models.
- To compare MPEP's effects with established anxiolytics, diazepam and buspirone.
Main Methods:
- Rodent models of conditioned anxiety: fear-potentiated startle (FPS), conditioned ultrasonic vocalization (USV), and the modified Geller-Seifter procedure.
- Administration of MPEP, diazepam, and buspirone to assess anxiolytic-like activity.
Main Results:
- MPEP and diazepam, but not buspirone, exhibited anxiolytic-like effects in the FPS model.
- MPEP, diazepam, and buspirone similarly reduced ultrasonic vocalizations in the USV model.
- All three compounds increased punished responses in the modified Geller-Seifter procedure, indicating anxiolytic-like activity.
Conclusions:
- MPEP demonstrates consistent anxiolytic-like effects across various conditioned anxiety models.
- Targeting mGluR5 receptors represents a promising novel therapeutic strategy for anxiety disorders.
More Related Videos
Related Concept Videos
01:29Anxiolytic Drugs: Benzodiazepines and Buspirone
01:26Anxiolytic Drugs: Overview
Primary Types of Anxiolytic Drugs
1. Benzodiazepines:
Benzodiazepines bind to the GABA-A receptor in the brain, enhancing GABA's interaction. This action reduces neurotransmission, effectively blocking anxiety-associated limbic circuitry.
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
01:19Sedatives and Hypnotics Drugs: Benzodiazepines
Benzodiazepines work by enhancing the effects of the inhibitory neurotransmitter GABA. They bind to the GABAA receptor, increasing its affinity for GABA, which opens chloride...
01:23Sedatives and Hypnotics: Overview
Sedative-hypnotics are categorized into barbiturates, benzodiazepines (BZDs), and non-benzodiazepines or Z-drugs. These drugs work by suppressing central nervous system activity, and this suppression is dose-dependent. Older sedative medications, like barbiturates, follow a linear curve in...