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June 26, 2026ACS Chemical NeuroscienceOpen Access

Discovery of VU6066098: A Selective and CNS-Penetrant mGlu 2 NAM with Robust Antidepressant-, Antipsychotic-, and Procognitive-like Activity in Rodents

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Authors

JCJeremy S. ColemanRCRory A. CapstickSCSichen Chang

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Overview

Randomized trial shows VU6066098 induces robust antidepressant and cognitive effects in rodent models, suggesting therapeutic potential.

Key Points

  • This research aims to develop a novel mGlu2 negative allosteric modulator for treating psychiatric disorders.
  • Used VU6066098 in preclinical rat models to assess its effects on depression, cognition, and psychosis.
  • Evaluated pharmacokinetic properties including clearance and half-life.
  • Conducted behavioral assays including forced swim tests and cognitive tasks.
  • VU6066098 showed an oral minimum effective dose of 1 mg/kg for antidepressant effects, matching ketamine.
  • Demonstrated dose-dependent cognitive enhancements at minimum effective doses of 3 mg/kg for recognition tasks.
  • Sustained effects on cognitive performance were observed up to 30 days following a 10 mg/kg dose in a TBI model.

Cite This Study

Coleman et al. (2026) studied this question.

synapsesocial.com/papers/6a3e16cd030ad1a9b30907b3https://doi.org/10.1021/acschemneuro.6c00324
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