A Systematic Review of the Effects of N-Methyl-D-Aspartate Receptor Antagonists on Pancreatic Islets
Sabrina Wong, Gia Han Le, Jens Uhlig, Ellen Yang, Christine E. Dri, Joshua D. Rosenblat, Rodrigo B. Mansur, Roger S. McIntyre
Neuroendocrinology October 30, 2025 DOI: 10.1159/000549276 via OpenAlex
Summary
AI-generated from the abstractBlocking NMDA receptors improves the function and survival of pancreatic alpha and beta cells, which may help explain why certain NMDA antagonists like ketamine, esketamine, and dextromethorphan have antidepressant effects and could also address metabolic problems often seen in depression. The findings suggest a shared mechanism linking mood regulation and pancreatic hormone control. More research is needed on how low doses of these drugs affect pancreatic function and delta cells.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Alpha cell Pancreatic islets Nmda receptor Antagonism Antidepressant |
| Key finding | NMDAR antagonism improves alpha and beta cell function and viability, potentially linking antidepressant effects to improved metabolic health in depression. |
Abstract
Our results suggest that NMDAR antagonism improves alpha and beta cell function and viability, which may have translational relevance to comorbid metabolic dysfunction in depression. These mechanisms may subserve the antidepressant effects of select NMDA antagonists (e.g., ketamine/esketamine, dextromethorphan). Further research should aim to investigate the effects of subanesthetic doses of ketamine/esketamine on pancreatic function and on delta cells. .