Assessment of the potential of novel and classical opioids to induce respiratory depression in mice
Rattachement africain : gb, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND AND PURPOSE: Opioid-induced respiratory depression limits the use of μ-opioid receptor agonists in clinical settings and is the main cause of opioid overdose fatalities. The relative potential of different opioid agonists to induce respiratory depression at doses exceeding those producing analgesia is understudied despite its relevance to assessments of opioid safety. Here we evaluated the respiratory depressant and anti-nociceptive effects of three novel opioids and relate these measurements to their in vitro efficacy. EXPERIMENTAL APPROACH: Respiration was measured in awake, freely moving male CD-1 mice using whole body plethysmography. Anti-nociception was measured using the hot plate test. Morphine, oliceridine and tianeptine were administered intraperitoneally, whereas methadone, oxycodone and SR-17018 were administered orally. Receptor activation and arrestin-3 recruitment were measured in HEK293 cells using BRET assays. KEY RESULTS: Across the dose ranges examined, all opioids studied depressed respiration in a dose-dependent manner, with similar effects at the highest doses, and with tianeptine and oliceridine showing reduced duration of effect, when compared with morphine, oxycodone, methadone and SR-17018. When administered at doses that induced similar respiratory depression, all opioids induced similar anti-nociception, with tianeptine and oliceridine again showing reduced duration of effect. These data were consistent with the in vitro agonist activity of the tested compounds. CONCLUSION AND IMPLICATIONS: In addition to providing effective anti-nociception, the novel opioids, oliceridine, tianeptine and SR-17018 depress respiration in male mice. However, the different potencies and kinetics of effect between these novel opioids may be relevant to their therapeutic application in different clinical settings.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Assessment of the potential of novel and classical opioids to induce respiratory depression in mice
- Date Crossref
- 22/08/2023
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Nottingham pays non établi dans la noticeUniversité ou école supérieure
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Queen's Medical Centre pays non établi dans la noticeÉtablissement de santé
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Columbia University Department of Chemistry pays non établi dans la noticeUniversité ou école supérieure
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New York Psychoanalytic Society and Institute pays non établi dans la noticeInstitution
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New York State Psychiatric Institute Division of Molecular Therapeutics pays non établi dans la noticeÉtablissement de santé
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Centre of Membrane Proteins and Receptors pays non établi dans la noticeInstitution
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School of Life Sciences Pharmacology and Neuroscience pays non établi dans la noticeUniversité ou école supérieure
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School of Pharmacy Division of Biomolecular Science and Medicinal Chemistry pays non établi dans la noticeUniversité ou école supérieure
University of Nottingham, Queen's Medical Centre et Department of Chemistry — Columbia University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.