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Shigeyuki Chaki

2 papers in the library · 116 citations · publishing 2016-2023

Papers

Rapid and Sustained Antidepressant Action of the mGlu2/3 Receptor Antagonist MGS0039 in the Social Defeat Stress Model: Comparison with Ketamine

The International Journal of Neuropsychopharmacology October 7, 2016 Chao Dong, Ji-Chun Zhang, Wei Yao et al. 116 citations

MGS0039, a metabotropic glutamate 2/3 receptor antagonist, produces rapid and sustained antidepressant effects in mice subjected to social defeat stress, similar to the well-known antidepressant ketamine. A single dose of either drug reversed depression-like behaviors—reducing immobility in tail suspension and forced swimming tests within 1–2 days and restoring sucrose preference over 3–7 days. Both compounds also reversed reductions in brain-derived neurotrophic factor, TrkB signaling, glutamate receptor subunits, and spine density in the prefrontal cortex, dentate gyrus, and CA3 region of the hippocampus, but not in the nucleus accumbens. These findings suggest that MGS0039 may offer a novel antidepressant mechanism through lasting synaptic changes in specific brain regions.

DOI: 10.1093/ijnp/pyw089 (opens in new tab) Ketamine Dentate gyrus Prefrontal cortex Brain-derived neurotrophic factor +13

Antidepressants in the post-ketamine Era: Pharmacological approaches targeting the glutamatergic system.

Neuropharmacology February 1, 2023 Shigeyuki Chaki, Mai Watanabe

The limited efficacy of current antidepressants has driven research into the glutamatergic system as a drug target for depression, validated by ketamine's antidepressant effects and leading to the approval of esketamine (Spravato®). However, ketamine and esketamine have adverse effects that limit routine use. Understanding ketamine's mechanisms has spurred drug discovery for agents with similar efficacy but fewer side effects. Efforts include identifying active circulating substances after ketamine administration and agents targeting its mechanisms. Clinical trials are ongoing, and in 2022, AUVELITY™ (dextromethorphan with bupropion) was FDA-approved. Future development aims for safer, rapidly acting antidepressants as potent as ketamine.

DOI: 10.1016/j.neuropharm.2022.109348 (opens in new tab) Full text (opens in new tab) Depression Ketamine Antidepressant Drug discovery +2