Breakthrough Depression Treatment: KNT-127 Shows Promise as Rapid-Acting Antidepressant
January 15, 2025
The global burden of anxiety and depression-related disorders is on the rise, underscoring the urgent need for new therapeutic agents that act quickly and have fewer side effects.
Current medications for anxiety and depression often suffer from limitations such as slow onset of action and adverse long-term effects, creating a demand for innovative therapies.
Recent research conducted by Professor Akiyoshi Saitoh and his team at Tokyo University of Science has highlighted the potential of delta opioid receptor (DOP) agonists, particularly KNT-127, as effective treatments for depression.
Their study, published in Molecular Psychiatry, uncovers the molecular and cellular mechanisms behind the antidepressant-like effects of KNT-127.
Molecular analysis revealed that KNT-127's antidepressant effects are primarily mediated by Akt signaling in the medial prefrontal cortex (mPFC), while its anxiolytic effects are linked to ERK signaling in the amygdala.
Local injection of KNT-127 into the infralimbic cortex, analogous to Brodmann Area 25 in humans, produced antidepressant effects through the PI3K and mTOR pathways.
The study also found that the mechanistic target of rapamycin (mTOR) signaling pathway plays a crucial role in mediating the effects of KNT-127, as its inhibition reversed the antidepressant-like effects.
KNT-127 enhances glutamatergic transmission in isolated IL-PFC brain tissue by suppressing GABA release, illustrating its direct action on this area.
The research indicates that DOPs are expressed in parvalbumin-positive interneurons in the IL-PFC, providing new insights into their mechanisms of action in mood regulation.
The antidepressant effects of KNT-127 were consistent across different mouse strains, ages, and sexes, indicating broad therapeutic potential for DOP agonists.
Professor Saitoh emphasized that their findings support the clinical development of DOP agonists as effective treatments for depression, particularly for patients who are resistant to conventional therapies.
The findings suggest that DOP agonists like KNT-127 may offer a new treatment option for patients resistant to conventional antidepressants, potentially revolutionizing depression treatment.
Summary based on 2 sources
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ScienceDaily • Jan 14, 2025
Scientists uncover rapid-acting, low-side-effect antidepressant target
Medical Xpress • Jan 14, 2025
Scientists uncover rapid-acting, low-side-effect antidepressant target