Glutamatergic receptor and neuroplasticity in depression: Implications for ketamine and rapastinel as the rapid-acting antidepressants.
Ya-Ting Wang, Ning-Ning Zhang, Ling Liu, Hong Jiang, Die Hu, Zhen-Zhen Wang, N. Chen, Yi Zhang
Biochemical and Biophysical Research Communications - BBRC January 1, 2022 DOI: 10.1016/j.bbrc.2022.01.024 via Semantic Scholar
Summary
Ketamine, an NMDAR antagonist, and rapastinel, an NMDAR positive allosteric modulator, both produce rapid and sustained antidepressant effects, but rapastinel lacks ketamine's severe side effects. Their shared antidepressant action converges on the BDNF and mTORC1 signaling pathways, which promote synaptic plasticity. This suggests that targeting downstream synaptic processes could guide the development of next-generation rapid-acting antidepressants.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Medicine |
| Citations | 47 |
| Key finding | Ketamine and rapastinel share convergent antidepressant mechanisms through BDNF and mTORC1 pathways in synaptic plasticity. |
Abstract
PURPOSE OF REVIEW To explore the convergent downstream pathways of ketamine and rapastinel and drive further development of identification for following generational rapid-acting antidepressants in the synaptic process. RECENT FINDINGS Ketamine is an NMDAR antagonist and is proven effective in depression for the rapid and sustained antidepressant response, while rapastinel is an NMDAR positive allosteric modulator, producing antidepressant effects like ketamine with no severe side effects. The common antidepressant effects of ketamine and rapastinel are BDNF and mTORC1 pathway in synaptic plasticity.