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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 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Keywords Alpha cell Pancreatic islets Nmda receptor Antagonism Antidepressant Beta cell Function biology Endocrinology Pharmacology Receptor antagonist Adrenergic receptor Pathophysiology Pancreatic function Diabetes mellitus Mechanism of action Pancreatic hormone Insulin
Key findings 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. .