Discovery of Rapid-Acting, Orally Available Antidepressants by Activating TrkB Signaling.
Journal of medicinal chemistry July 29, 2025 Xu Cheng, Fan Jiang, Lixin Liu et al. 1 citation
A new compound, B11, shows promise as a rapid-acting antidepressant in preclinical models. Unlike existing fast-acting treatments such as esketamine and psychedelics, which carry risks of psychotic side effects and substance abuse, B11 activates the TrkB-CREB signaling axis without interfering with targets linked to those side effects. B11 readily crosses the blood-brain barrier and has a favorable pharmacokinetic profile allowing oral administration. These findings highlight the potential for optimized fast-onset antidepressants to address unmet needs in treating major depressive disorder and underscore the role of neuroplasticity modulation in drug discovery.