Related Experiment Video
Updated: May 14, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Pharmacology of metabotropic glutamate receptor allosteric modulators: structural basis and therapeutic potential for
Karen J Gregory1, Meredith J Noetzel, Colleen M Niswender
1Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract:
The metabotropic glutamate receptors (mGlus) mediate a neuromodulatory role throughout the brain for the major excitatory neurotransmitter, glutamate. Seven of the eight mGlu subtypes are expressed within the CNS and are attractive targets for a variety of psychiatric and neurological disorders including anxiety, depression, schizophrenia, Parkinson's disease, and Fragile X syndrome. Allosteric modulation of these class C 7-transmembrane spanning receptors represents a novel approach to facilitate development of mGlu subtype-selective probes and therapeutics. Allosteric modulators that interact with sites topographically distinct from the endogenous ligand-binding site offer a number of advantages over their competitive counterparts. In particular for CNS therapeutics, allosteric modulators have the potential to maintain the spatial and temporal aspects of endogenous neurotransmission. The past 15 years have seen the discovery of numerous subtype-selective allosteric modulators for the majority of the mGlu family members, including positive, negative, and neutral allosteric modulators, with a number of mGlu allosteric modulators now in clinical trials.
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Antiepileptic Drugs: Glutamate Antagonists
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...

