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. 2025 Aug 8;16:1621887. doi: 10.3389/fpsyt.2025.1621887

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Copyright © 2025 Uyar and Gonul.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Pathways targeted by new antidepressants include NMDA receptor antagonism by Ketamine and Esketamine, Sigma-1 receptor agonism by Dextromethorphan, GABA-A receptor modulation by Brexanolone and Zuranolone, and Kappa receptor antagonism by Esmethadone, all affecting BDNF. — Mechanisms of action of novel antidepressants discussed in this review, including NMDA receptor modulation, GABA-A receptor potentiation, and multimodal serotonergic activity.