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Updated: Oct 22, 2025

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Positive allosteric modulators (PAMs) of the group II metabotropic glutamate receptors: Design, synthesis, and
Yousuke Yamada1, Kristen Gilliland2, Zixiu Xiang2
1Warren Center for Neuroscience Drug Discovery at Vanderbilt University, Vanderbilt University, Nashville, TN 37232, USA.
Abstract:
This letter describes synthesis and evaluation of two series of dual mGlu2/mGlu3 positive allosteric modulators with moderate mGlu3 potency and robust mGlu2 potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu3-mediated signaling in central neurons by co-application of a selective mGlu2 NAM to isolate mGlu3-selective effects. Using acute mouse brain slices from the prefrontal cortex, potentiation of group II mGlu receptor agonist Ca2+ signaling in PFC pyramidal cells with either the dual mGlu2/mGlu3 PAM 16e or 23d demonstrated effects mediated selectively via mGlu3.
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