Ketamine – More mechanisms of action than just NMDA blockade
Trends in Anaesthesia and Critical Care March 22, 2014 Jamie Sleigh, Martyn Harvey, Logan J. Voss et al. 441 citations
Ketamine 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.