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Novel mechanisms underlying rapid-acting antidepressants: ketamine-like compounds, neurosteroid GABAkines, and psychedelics.

Sara Castanheira, Catarina Vale Gomes, Joana Bicker, Ana Fortuna

Drug Discovery Today June 1, 2025 DOI: 10.1016/j.drudis.2025.104371 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Ketamine Esketamine
Keywords Bdnf Gaba Psychedelics Rapid-acting antidepressant drug Depression treatment Neuroscience research Antidepressant drugs Brain chemistry Mental health therapy
Citations 9
Key findings Rapid-acting antidepressant drugs primarily work by potentiating BDNF or activating GABAA receptors.

Abstract

The discovery of the rapid antidepressant action of ketamine accelerated the identification of new molecules that are associated with fast and prolonged relief of depressive symptoms. As a result, a new group of antidepressants have emerged, some of them already approved for clinical use, classified as rapid-acting antidepressant drugs (RAADs). Potentiation of brain-derived neurotrophic factor (BDNF) or activation of the GABAA receptors are the main mechanisms behind the notable properties of RAADs, a mainstream topic in the field of pharmacology and drug discovery that deserves an updated review.

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