Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence

  title={Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence},
  author={Jolanta Helena Kotlinska and Juergen Wichmann and Piotr Rafalski and Sylwia Talarek and Tomasz Dylag and Jerzy Silberring},
The non-peptidergic opioid receptor-like 1 (ORL1, OP4) receptor ligand, Ro 64-6198 {(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one}, is a full agonist of the OP4 receptor. The aim of this study was to evaluate whether this compound influences morphine antinociception and dependence in mice. Ro 64-6198 inhibits the acute analgesic effect of morphine in the tail-immersion test, however, when given chronically during the acquisition of morphine… 

Comparison of the Antinociceptive and Antirewarding Profiles of Novel Bifunctional Nociceptin Receptor/μ-Opioid Receptor Ligands: Implications for Therapeutic Applications

It is suggested that NOPr full-agonist activity is required to modulate opioid-induced reward, whereas a bifunctional Nopr/MOPr partial agonist profile may be suitable as a nonaddicting analgesic.

Involvement of the nociceptin opioid peptide receptor in morphine-induced antinociception, tolerance and physical dependence in female mice.

It is demonstrated that N/OFQ-NOP receptor system plays diverse roles in modulating pharmacological profiles of µ-opioid receptor agonists and that opioid analgesia has sex differences, and females experience greater pain and consume more opioids.

The Nociceptin Receptor (NOP) Agonist AT-312 Blocks Acquisition of Morphine- and Cocaine-Induced Conditioned Place Preference in Mice

Results show that small-molecule NOP receptor agonists have promising efficacy for attenuating the rewarding effects of morphine and cocaine, and may have potential as pharmacotherapy for opioid and psychostimulant addiction or for treating polydrug addiction.

The nociceptin/orphanin FQ receptor (NOP) as a target for drug abuse medications.

  • N. Zaveri
  • Biology, Psychology
    Current topics in medicinal chemistry
  • 2011
As with the case of buprenorphine, a mixed-action profile of NOP/opioid activity may provide a more effective drug to treat addiction to various abused substances and/or polydrug addiction.

[Nociceptin/orphanin FQ (N/OFQ)--the opioid, antiopioid or neuromodulator?].

The aim of this review was to present current opinion on the role of N/OFQ in nociception, reward and drug dependence.

The pharmacology of Ro 64-6198, a systemically active, nonpeptide NOP receptor (opiate receptor-like 1, ORL-1) agonist with diverse preclinical therapeutic activity.

Preclinical data indicate that Ro 64-6198 may have broad clinical uses, such as in treating stress and anxiety, addiction, neuropathic pain, cough, and anorexia, and it has subnanomolar affinity for the NOP receptor and is at least 100 times more selective for theNOP receptor over the classic opioid receptors.



A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat.

These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphan in F Q/nOCiceptin in adaptive behavioral fear responses to stress.

Orphanin FQ acts as a supraspinal, but not a spinal, anti‐opioid peptide

The findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites, and not to systemic morphine antinociception induced by i.c.t. morphine.

Pharmacological characterization of the nociceptin receptor mediating hyperalgesia in the mouse tail withdrawal assay

These results demonstrate that both the direct hyperalgesic action and the anti‐morphine effect of NC can be studied under the same experimental conditions in the mouse tail withdrawal assay, and indicates the existence of important differences between peripheral and central NC receptors.

The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats

It is shown here that neither Ro 64-6198 nor alprazolam exhibited rewarding or aversive properties, whereas morphine induced a pronounced CPP, suggesting that this new class of anxiolytic drugs is devoid of the risk for potential non-medical use and dependence.