How fast-acting antidepressants work at the molecular level and new ideas for developing them

Ketamine may produce rapid antidepressant effects by influencing multiple synaptic targets.

• Conventional antidepressants often require several weeks to show significant effects, and about two-thirds of patients may not respond effectively.
• Ketamine's antidepressant action involves not only NMDA receptor antagonism but also affects other receptors and channels in the synapse.
• The mechanisms of ketamine include effects on α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and L-type calcium channels.
• Psilocybin, a 5-HT2A receptor agonist, has shown potential for rapid antidepressant effects in both mouse models and clinical studies.
• The review highlights emerging pharmacological targets for rapid-acting antidepressants, suggesting new directions for future research.

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