Current and Future Therapeutic Options in Pain Management: Multi-mechanistic Opioids Involving Both MOR and NOP Receptor Activation.
Journal
CNS drugs
ISSN: 1179-1934
Titre abrégé: CNS Drugs
Pays: New Zealand
ID NLM: 9431220
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
accepted:
18
04
2022
pubmed:
27
5
2022
medline:
9
6
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
Opioids are widely used in chronic pain management, despite major concerns about their risk of adverse events, particularly abuse, misuse, and respiratory depression from overdose. Multi-mechanistic opioids, such as tapentadol and buprenorphine, have been widely studied as a valid alternative to traditional opioids for their safer profile. Special interest was focused on the role of the nociceptin opioid peptide (NOP) receptor in terms of analgesia and improved tolerability. Nociceptin opioid peptide receptor agonists were shown to reinforce the antinociceptive effect of mu opioid receptor (MOR) agonists and modulate some of their adverse effects. Therefore, multi-mechanistic opioids involving both MOR and NOP receptor activation became a major field of pharmaceutical and clinical investigations. Buprenorphine was re-discovered in a new perspective, as an atypical analgesic and as a substitution therapy for opioid use disorders; and buprenorphine derivatives have been tested in animal models of nociceptive and neuropathic pain. Similarly, cebranopadol, a full MOR/NOP receptor agonist, has been clinically evaluated for its potent analgesic efficacy and better tolerability profile, compared with traditional opioids. This review overviews pharmacological mechanisms of the NOP receptor system, including its role in pain management and in the development of opioid tolerance. Clinical data on buprenorphine suggest its role as a safer alternative to traditional opioids, particularly in patients with non-cancer pain; while data on cebranopadol still require phase III study results to approve its introduction on the market. Other bifunctional MOR/NOP receptor ligands, such as BU08028, BU10038, and AT-121, are currently under pharmacological investigations and could represent promising analgesic agents for the future.
Identifiants
pubmed: 35616826
doi: 10.1007/s40263-022-00924-2
pii: 10.1007/s40263-022-00924-2
pmc: PMC9166888
doi:
Substances chimiques
Analgesics, Opioid
0
BU10038
0
Isoquinolines
0
Opioid Peptides
0
Phenylpropionates
0
Receptors, Opioid, mu
0
Buprenorphine
40D3SCR4GZ
Naltrexone
5S6W795CQM
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
617-632Informations de copyright
© 2022. The Author(s).
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