Anesthesiology
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Cebranopadol is a novel strong analgesic that coactivates the nociceptin/orphanin FQ receptor and classical opioid receptors. There are indications that activation of the nociceptin/orphanin FQ receptor is related to ceiling in respiratory depression. In this phase 1 clinical trial, we performed a pharmacokinetic-pharmacodynamic study to quantify cebranopadol's respiratory effects. ⋯ At the dose tested, cebranopadol produced respiratory depression with an estimate for minimum ventilation greater than 0 l/min. This is a major advantage over full μ-opioid receptor agonists that will produce apnea at high concentrations. Further clinical studies are needed to assess whether such behavior persists at higher doses.
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The "dissociative " general anesthetic ketamine is a well-known N-methyl-D-aspartate receptor antagonist. However, whether ketamine, at clinically relevant concentrations, increases the activity of inhibitory γ-aminobutyric acid (GABA) receptor type A (GABAA) receptors in different brain regions remains controversial. Here, the authors studied the effects of ketamine on synaptic and extrasynaptic GABAA receptors in hippocampal neurons. Ketamine modulation of extrasynaptic GABAA receptors in cortical neurons was also examined. ⋯ Clinically relevant concentrations of ketamine increased the activity of high-affinity extrasynaptic GABAA receptors in the hippocampus and cortex, an effect that likely contributes to ketamine's neurodepressive properties.