The nociceptin/orphanin FQ (NOP) receptor antagonist J‐113397 enhances the effects of levodopa in the MPTP‐lesioned nonhuman primate model of Parkinson's disease

  title={The nociceptin/orphanin FQ (NOP) receptor antagonist J‐113397 enhances the effects of levodopa in the MPTP‐lesioned nonhuman primate model of Parkinson's disease},
  author={Naomi P. Visanji and Rob M.A. de Bie and Tom H. Johnston and Andrew C McCreary and Jonathan M. Brotchie and Susan H. Fox},
  journal={Movement Disorders},
The anti‐parkinsonian and levodopa‐sparing potential of the nociceptin/orphanin FQ receptor (NOP) antagonist J‐113397 has been demonstrated in rodent models of Parkinson's disease. Here, we describe the levodopa‐sparing potential of J‐113397 in MPTP‐lesioned marmosets. Coadministration of J‐113397 (30 mg/kg) with a sub‐therapeutic dose of levodopa (12.5 mg/kg) produced an anti‐parkinsonian action equivalent to that of a therapeutic dose of levodopa. However, these effects were accompanied by an… 
Acute and chronic antiparkinsonian effects of the novel nociceptin/orphanin FQ receptor antagonist NiK‐21273 in comparison with SB‐612111
The acute and long‐term antiparkinsonian effects of the novel compound 2‐[3‐[4‐(2‐chloro‐6‐fluoro‐phenyl)‐piperidin‐1‐ylmethyl]‐2‐(morpholine‐4‐carbonyl)‐indol‐ 1‐yl]‐acetamide (NiK‐21273) in comparison with the potent and selective NOP receptor antagonist SB‐612111 is reported.
Activation of Nociceptin/Orphanin FQ Peptide Receptors Disrupts Visual but Not Auditory Sensorimotor Gating in BALB/cByJ Mice: Comparison to Dopamine Receptor Agonists
Results show that pharmacological stimulation of NOP or dopamine D2-like receptors is more potent in disrupting visual than acoustic PPI in mice, whereas D1-like receptor activation disrupts both, and suggest that dysfunction of N/OFQ transmission may be implicated in the pathogenesis of psychotic manifestations.
Nociceptin/Orphanin FQ Inhibits the Survival and Axon Growth of Midbrain Dopaminergic Neurons Through a p38-MAPK Dependent Mechanism
It is demonstrated for the first time that N/OFQ is detrimental to the survival and growth of dopaminergic neurons and that its expression is altered in the midbrain of patients with Parkinson’s disease.
NOP Receptor Ligands and Parkinson's Disease.
This chapter presents data showing that, in addition to motor symptoms, N/OFQ also plays a role in the parkinsonian neurodegeneration, and NOP receptor antagonists possess neuroprotective/neurorescue properties in in vitro and in vivo models of PD.
Potential of Nociceptin/Orphanin FQ Peptide Analogs for Drug Development
The structure of potent peptide‐based agonists, antagonists, biased analogs and bivalent ligands that target NOP receptor are reviewed to fully understand the role of NOP‐N/OFQ system in the body and may lead to designing novel therapeutics.
UFP‐112 a Potent and Long‐Lasting Agonist Selective for the Nociceptin/Orphanin FQ Receptor
The present review article summarizes data from the literature and presents original findings on the in vitro and in vivo pharmacological features of UFP‐112 to discuss important biological actions and possible therapeutic indications of NOP receptor agonists.
Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility.
  • N. Zaveri
  • Biology, Medicine
    Journal of medicinal chemistry
  • 2016
The progress toward validating the NOP-N/OFQ system as a therapeutic target is discussed, suggesting that NOP agonists may have clinical utility for pain treatment and substance abuse pharmacotherapy.
Anti‐Parkinsonian and anti‐dyskinetic profiles of two novel potent and selective nociceptin/orphanin FQ receptor agonists
The efficacy of two novel, potent and chemically distinct NOP receptor agonists, AT‐390 and AT‐403, to improve Parkinsonian disabilities and attenuate dyskinesia development and expression are investigated.


The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway
By using a battery of behavioral tests, we showed that nociceptin/orphanin FQ receptor (NOP receptor) antagonists attenuated parkinsonian-like symptoms in 6-hydroxydopamine hemilesioned rats (Marti
Blockade of Nociceptin/Orphanin FQ Transmission Attenuates Symptoms and Neurodegeneration Associated with Parkinson's Disease
Evidence suggesting that endogenous N/OFQ may contribute to Parkinson's disease is presented and it is proposed that NOP receptor antagonists may represent a novel approach for combined (symptomatic and neuroprotective) therapy of Parkinson’s disease.
Nondopaminergic mechanisms in levodopa‐induced dyskinesia
  • J. Brotchie
  • Biology, Psychology
    Movement disorders : official journal of the Movement Disorder Society
  • 2005
It is speculated that the external globus pallidus and subthalamic nucleus may play distinct roles in different forms of dyskinesia, e.g., chorea/dystonia; peak/diphasic/off.
Pharmacological characterization of psychosis‐like behavior in the MPTP‐lesioned nonhuman primate model of Parkinson's disease
By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, it is found that the pharmacology of these behaviors recapitulates, in several respects, the Pharmacology of psychosis inPD.
Levodopa‐induced dyskinesias
This review focuses on three issues related to Levodopa‐induced dyskinesia: clinical features, classification and rating, pathophysiology and pathogenesis, and management.
Novel pharmacological targets for the treatment of Parkinson's disease
This review describes the important recent advances that underlie the development of novel dopaminergic and non-dopaminergic drugs for Parkinson's disease, and also for the motor complications that arise from the use of existing therapies.
Histamine H3 receptor agonists reduce L‐dopa–induced chorea, but not dystonia, in the MPTP‐lesioned nonhuman primate model of Parkinson's disease
The results obtained in this study suggest that histamine H3 receptors may be involved in the neural mechanisms underlying L‐dopa–induced dyskinesia in Parkinson's disease.
Blockade of Nociceptin/Orphanin FQ Receptor Signaling in Rat Substantia Nigra Pars Reticulata Stimulates Nigrostriatal Dopaminergic Transmission and Motor Behavior
It is concluded that NOP receptors in the substantia nigra pars reticulata, activated by endogenous N/OFQ, drive a physiologically inhibitory control on motor behavior, possibly via modulation of the nigrostriatal dopaminergic pathway.