TAK-925 (Danavorexton), an Orexin Receptor 2 Agonist, Reduces Opioid-induced Respiratory Depression and Sedation without Affecting Analgesia in Healthy Men.

Background: Orexin neuropeptides help regulate sleep/wake states, respiration, and pain. However, their potential role in regulating breathing, particularly in perioperative settings, is not well understood. TAK-925 (danavorexton), a novel orexin receptor 2-selective agonist, directly activates neurons associated with respiratory control in the brain and improves respiratory parameters in rodents undergoing fentanyl-induced sedation.

Acute effects of esketamine on hypoxic ventilatory response, haemodynamics, and brain function in healthy volunteers.

Background: The acute hypoxic ventilatory response is a critical chemoreflex originating at the carotid bodies. This study investigates the impact of low-dose i.v.

Nitric Oxide Donor Sodium Nitroprusside Reduces Racemic Ketamine-But Not Esketamine-Induced Pain Relief.

The anesthetic, analgesic and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following -methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial.

Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial.

Background: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion.

Opioid-free anesthesia: A systematic review and meta-analysis.

Study Objective: To evaluate all available evidence thus far on opioid based versus opioid-free anesthesia and its effect on acute and chronic postoperative pain.

Design: Systematic review and meta-analysis of randomized clinical trials.

Setting: Operating room, postoperative recovery room and ward.

Inhaled Δ-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers.

Background: In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined.

Respiratory Effects of Biased Ligand Oliceridine in Older Volunteers: A Pharmacokinetic-Pharmacodynamic Comparison with Morphine.

Background: Oliceridine is a G protein-biased µ-opioid, a drug class that is associated with less respiratory depression than nonbiased opioids, such as morphine. The authors quantified the respiratory effects of oliceridine and morphine in elderly volunteers. The authors hypothesized that these opioids differ in their pharmacodynamic behavior, measured as effect on ventilation at an extrapolated end-tidal Pco2 at 55 mmHg, V̇E55.

Buprenorphine: a treatment and cause of opioid-induced respiratory depression.

Buprenorphine is a partial agonist at the mu opioid receptor. Due to its relatively low maximum effect on respiratory depression it is considered by some to be a safe opioid. But it can produce serious respiratory depression, particularly when combined with sedatives such as benzodiazepines.