NP-16 K2P Channels and NMDA Receptor as New Targets of Fast Onset Antidepressants

NP-16 K2P Channels and NMDA Receptor as New

Targets of Fast Onset Antidepressants

LI Yang; GUO Fei; MA Yu-qin

【期刊名称】《《神经药理学报》》 【年(卷),期】2024(008)004

【摘要】Major depressive disorder(MDD)is a common neuropsychiatric disorder characterized by diverse symptoms.There are big limitations of clinic medicine which highlighted an urgent and clear need for more efficacious and faster-acting therapeutic agents to treat patients with MDD,especially those who are refractory to the traditional antidepressants.In the present study,we assessed a novel compound,YY-21,from

timosaponin

B-Ⅲderived

from

sarsasapogenin

of

Anemarrhenae Rhizoma.We found that YY-21 obviously increased presynaptic glutamate release and enhanced long-term synaptic activity within 10 minutes as determined by excitatory postsynaptic current(EPSC)and field excitatory postsynaptic potential(fEPSP)in medial prefrontal cortex(mPFC)slices.YY-21 demonstrated anxiolytic-like effects following acute administration in animals and reversed the depressive-like and anxiety phenotypes induced by chronic unpredictable mild stress(CMS)with a relatively fast therapeutic onset.Our mechanism research reveals that NMDA receptors and K2P(TREK1)channels emerged as new drug targets for faster acting antidepressants.Two-pore