Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain

  title={Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain},
  author={Kinga Sałat and A. J. Furgala and Robert Sałat},
  pages={361 - 374}
BackgroundCebranopadol (a.k.a. GRT-6005) is a dually acting nociceptin/orphanin FQ and opioid receptor agonist that has been recently developed in Phase 2 clinical trials for painful diabetic neuropathy or cancer pain. It also showed analgesic properties in various rat models of pain and had a better safety profile as compared to equi-analgesic doses of morphine. Since antinociceptive properties of cebranopadol have been studied mainly in rat models, in the present study, we assessed analgesic… 

Comparison of Bromhexine and its Active Metabolite - Ambroxol as Potential Analgesics Reducing Oxaliplatin-Induced Neuropathic Pain - Pharmacodynamic and Molecular Docking Studies.

The conversion of bromhexine to other than ambroxol active metabolites should be considered when interpreting some of its in vivo effects, including their ability to attenuate pain caused by oxaliplatin.

Cebranopadol: A Novel First-in-Class Potent Analgesic Acting via NOP and Opioid Receptors.

Data is reviewed on the preclinical in vitro and in vivo pharmacology, safety, and tolerability, as well as clinical trials with cebranopadol, demonstrating efficacy and good tolerability in acute and chronic pain conditions.

KM-408, a novel phenoxyalkyl derivative as a potential anticonvulsant and analgesic compound for the treatment of neuropathic pain.

A novel compound, R,S-2-((2-chloro-6-methylphenoxy)ethyl)amino)butan-1-ol hydrochloride (KM-408) with dual antiseizure and analgesic activity has been developed for potential use in neuropathic pain treatment.

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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.

Cebranopadol as a Novel Promising Agent for the Treatment of Pain

Cebranopadol acts on the mu opioid receptor and the nociceptin/orphanin receptor and these receptors co-activation can reduce opioid side-effects without compromising analgesia.

The effect of analgesics on stimulus evoked pain-like behaviour in animal models for chemotherapy induced peripheral neuropathy- a meta-analysis

Chemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no

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New functionalized amino acids are designed and synthesized as inhibitors of GABA uptake and assessed their activities toward all four mouse GAT subtypes and it is pointed out that none of the test compounds induced motor deficits in the rotarod test.



Cebranopadol: a first-in-class potent analgesic agent with agonistic activity at nociceptin/orphanin FQ and opioid receptors

Cebranopadol is particularly interesting as a novel, potent bifunctional agonist of NOP/opioid receptors, the outcome of its ongoing and planned clinical trials will be crucial for its future development and potential application in humans.

Antihyperalgesic, Antiallodynic, and Antinociceptive Effects of Cebranopadol, a Novel Potent Nociceptin/Orphanin FQ and Opioid Receptor Agonist, after Peripheral and Central Administration in Rodent Models of Neuropathic Pain

Cebranopadol is effective after peripheral as well as central administration in nociceptive and chronic neuropathic pain and may be well‐suited for the treatment of chronic pain conditions with a neuropathic component.

Opioid-type Respiratory Depressant Side Effects of Cebranopadol in Rats Are Limited by Its Nociceptin/Orphanin FQ Peptide Receptor Agonist Activity

The therapeutic window between antinociception and respiratory depression in rats is larger for cebranopadol than that for fentanyl because the nociceptin/orphanin FQ peptide receptor agonist action of cebrantociceptive action counteracts side effects resulting from its &mgr;-opioid peptide receptors agonists action.

Cebranopadol: a first in-class example of a nociceptin/orphanin FQ receptor and opioid receptor agonist.

Modulation ofactivity at this receptor produces variable effects on the nociceptive (pain) response in laboratory animals, with N/OFQ and NOP agonists in general producing antinociception when given spinally and pro-nOCiceptive/anti-opioid actions when administered supraspinally in rodents.

Antinociceptive effects of the ORL1 receptor agonist nociceptin/orphanin FQ in diabetic mice.

Analgesic, anti-inflammatory, and antipyretic activity

The role of endogenous peptides such as enkephalines and endorphins gives more insight into brain processes and the action of central analgesics, as well as in vitro binding tests for animal experiments involving pain.