Asumir la ausencia

Nuckols, Anthony

doi:10.31819/9783968690261

Cited by 1 publication

(1 citation statement)

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“…The potent mu-opioid peptide (MOP) receptor agonists (i.e., morphine, oxycodone, and fentanyl) are the gold standard analgesics for relieving severe pain, whereas the clinical use of MOP agonists is restricted owing to their several adverse effects, such as reinforcing effects (abuse liability), respiratory depression, itch sensation, and constipation [70][71]. In the past few decades, several studies on classical opioid receptors enabled an advanced understanding of how opioid drugs act and exert beneficial and non-desirable effects [72][73][74].…”

Section: Benefits Of Bifunctional Nop/mop Ligandsmentioning

confidence: 99%

Nociceptin/Orphanin FQ Peptide Receptor-Related Ligands as Novel Analgesics

Kiguchi

Ding

Kishioka

et al. 2020

CTMC

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: Despite similar distribution patterns and intracellular events observed in the nociceptin/orphanin FQ peptide (NOP) receptor and other opioid receptors, NOP receptor activation displays unique pharmacological profiles. Several researchers have identified a variety of peptide and non-peptide ligands to determine the functional roles of NOP receptor activation and observed that NOP receptorrelated ligands exhibit pain modality-dependent pain processing. Importantly, NOP receptor activation results in anti-nociception and anti-hypersensitivity at the spinal and supraspinal levels regardless of the experimental settings in non-human primates (NHPs). Given that the NOP receptor agonists synergistically enhance mu-opioid peptide (MOP) receptor agonist-induced anti-nociception, it has been hypothesized that dual NOP and MOP receptor agonists may display promising functional properties as analgesics. Accumulating evidence indicates that the mixed NOP/opioid receptor agonists demonstrate favorable functional profiles. In NHP studies, bifunctional NOP/MOP partial agonists (e.g., AT-121, BU08028, and BU10038) exerted potent anti-nociception via NOP and MOP receptor activation; however, dose-limiting adverse effects associated with the MOP receptor activation, including respiratory depression, itch sensation, physical dependence, and abuse liability, were not observed. Moreover, a mixed NOP/opioid receptor agonist, cebranopadol, presented promising outcomes in clinical trials as a novel analgesic. Collectively, the dual agonistic actions on NOP and MOP receptors, with appropriate binding affinities and efficacies, may be a viable strategy to develop innovative and safe analgesics.

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Section: Benefits Of Bifunctional Nop/mop Ligandsmentioning

confidence: 99%