Ketamine – More mechanisms of action than just NMDA blockade
Jamie Sleigh, Martyn Harvey, Logan J. Voss, Bill Denny
Trends in Anaesthesia and Critical Care March 22, 2014 DOI: 10.1016/j.tacc.2014.03.002 via OpenAlex
Summary
AI-generated from the abstractKetamine has been used clinically for over 50 years, but its mechanisms remain largely unclear. Its hypnotic effects are mainly mediated by blocking NMDA and HCN1 receptors, while cholinergic, aminergic, and opioid systems modulate sedation and analgesia. Ketamine's effects on chronic pain and depression outlast drug levels, likely due to a secondary increase in synaptic connectivity triggered by a neuronal response to a hyper-glutamatergic state.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine |
| Keywords | Glutamatergic Nmda receptor Blockade Neuroscience |
| Citations | 441 |
| Key finding | Ketamine's long-lasting effects on chronic pain and depression are probably mediated by a secondary increase in structural synaptic connectivity from a neuronal response to a hyper-glutamatergic state. |
Abstract
Ketamine has been in clinical use for over half a century, yet its precise mechanisms of action remain mysterious for the large part. Its hypnotic effects appear to be largely mediated by blockade of NMDA and HCN1 receptors, but cholinergic, aminergic, and opioid systems appear to play both a positive and negative modulatory role in both sedation and analgesia. Ketamine's effects in chronic pain, and as an antidepressant, far outlast the actual drug levels, and are probably mediated by a secondary increase in structural synaptic connectivity that is mediated by a neuronal response to the ketamine-induced hyper-glutamatergic state.