Review
Biochemistry & Molecular Biology
Amal El Daibani, Tao Che
Summary: In our society today, pain has become a significant source of strain on individuals. Developing new pain treatments with fewer adverse effects is crucial. The NOP receptor has emerged as a promising focal point for novel pain therapies, offering an alternative to opioid morphine with potential life-threatening effects and addiction. This article reviews the molecular and cellular structure controlling the cellular trafficking of the NOP receptor and presents studies supporting its role in pain management.
Review
Biochemistry & Molecular Biology
Massimo Ubaldi, Nazzareno Cannella, Anna Maria Borruto, Michele Petrella, Maria Vittoria Micioni Di Bonaventura, Laura Soverchia, Serena Stopponi, Friedbert Weiss, Carlo Cifani, Roberto Ciccocioppo
Summary: Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that binds the NOP receptor and exerts anti-opioids effects; the NOP receptor is widely expressed in the brain, while N/OFQ is mainly localized in stress-related brain nuclei; preclinical evidence suggests that both NOP agonists and antagonists may be effective therapeutic approaches for substance use disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Stephen R. Morairty, Yu Sun, Lawrence Toll, Michael R. Bruchas, Thomas S. Kilduff
Summary: This study evaluated the effects of two NOPR agonists on sleep/wake in rats, mice, and Cynomolgus macaques. The results showed that these agonists increased non-Rapid Eye Movement sleep and electroencephalogram slow wave activity, while suppressing Rapid Eye Movement sleep in all three species. These findings suggest that the N/OFQ-NOPR system may have a previously unrecognized role in sleep/wake control and could be a potential therapeutic target for insomnia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Michael E. Meyer, Arpit Doshi, Willma E. Polgar, Nurulain T. Zaveri
Summary: The development of SAR around substituted N-piperidinyl indole-based nociceptin opioid receptor (NOP) ligands led to the discovery of a novel series of 2-substituted N-piperidinyl indoles that provide selective NOP full agonists and bifunctional NOP full agonists-Mu-opioid (MOP) receptor partial agonists. The SAR in this study reveals that 2-substitution on the indole moiety affects the intrinsic activity and opioid receptor selectivity of these compounds compared to the 3-substituted counterparts. Molecular docking of these compounds in NOP homology model and MOP receptor structures provides insights into the observed differences in binding, functional profiles, and selectivity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Mark F. Bird, Christopher P. Hebbes, Anushuya Tamang, Jonathon Mark Willets, Jonathan P. Thompson, Remo Guerrini, Girolamo Calo, David G. Lambert
Summary: In this study, the role of N/OFQ-NOP system was explored in freshly isolated volunteer human B- and T-cells incubated with LPS and PepG as a model of in vitro sepsis. The findings suggest that N/OFQ-NOP receptors play a regulatory role in B and T cell function, inhibiting cell migration and reducing GM-CSF release to variable degrees.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ana Domi, Veronica Lunerti, Michele Petrella, Esi Domi, Anna Maria Borruto, Massimo Ubaldi, Friedbert Weiss, Roberto Ciccocioppo
Summary: Genetic deletion or pharmacological blockade of NOP receptors have shown to reduce nicotine intake and motivation to self-administer in rats. The NOP receptor antagonist LY2817412 decreased nicotine intake in wild-type rats, confirming its effect is mediated by inhibition of NOP transmission. Injection of LY2817412 into the VTA decreased nicotine self-administration, suggesting that NOP receptor antagonism may be a potential treatment for smoking cessation.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ian B. Denys, Juan Gao, Jane C. Sutphen, Nurulain T. Zaveri, Daniel R. Kapusta
Summary: The study demonstrates that nonpeptide NOP agonists decrease blood pressure and produce diuresis, with AT-039 being a novel nonpeptide NOP agonist that lacks sedative and hyperphagic effects, making it potentially useful in the treatment of hypertension and/or volume overload/hyponatremia.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Geriatrics & Gerontology
Marco Raffaele, Kristina Kovacovicova, Tommaso Biagini, Oriana Lo Re, Jan Frohlich, Sebastiano Giallongo, James D. Nhan, Antonino Giulio Giannone, Daniela Cabibi, Martin Ivanov, Anton B. Tonchev, Martin Mistrik, Matthew Lacey, Petr Dzubak, Sona Gurska, Marian Hajduch, Jiri Bartek, Tommaso Mazza, Vincenzo Micale, Sean P. Curran, Manlio Vinciguerra
Summary: The study identified MCOPB as a NOP ligand with tissue-specific senolytic effects, reducing the senescent cell burden in peripheral tissues but not affecting the central nervous system. Additionally, exposure to MCOPB led to changes in locomotion and lipid storage. Mechanistically, MCOPB treatment activated transcriptional networks involved in immune responses to external stressors, implicating Toll-like receptors (TLRs).
Review
Pharmacology & Pharmacy
Omar N. Al Yacoub, Hibah O. Awwad, Yong Zhang, Kelly M. Standifer
Summary: This article reviews the role of the N/OFQ-NOP receptor system in the neurological and behavioral sequelae of PTSD and TBI. The current findings suggest that NOP modulators may have potential as therapeutics for these disorders and their co-morbidities. The authors advocate for the development of standards for common data elements reporting to improve reproducibility and data sharing.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Elaine C. Gavioli, Victor A. D. Holanda, Girolamo Calo, Chiara Ruzza
Summary: Resilience plays a crucial role in mental health, and understanding its mechanisms can improve treatment outcomes and help high-risk individuals. The N/OFQ-NOP system is central to stress response, affecting hormone secretion, behavior, and psychopathologies.
Article
Cell Biology
Qihui Guan, Renata Voltolini Velho, Alice Jordan, Sabrina Pommer, Irene Radde, Jalid Sehouli, Sylvia Mechsner
Summary: Endometriosis is a chronic inflammatory disease that affects millions of women worldwide. Chronic pelvic pain is a major issue in this condition, but current treatment options are not effective. Understanding pain mechanisms can help develop better therapeutic strategies, particularly specific analgesic options.
Article
Biochemistry & Molecular Biology
Guan-Yu Zhuo, Ming-Chi Chen, Tzu-Yu Lin, Shih-Ting Lin, Daniel Tzu-Li Chen, Cynthia Wei-Sheng Lee
Summary: We investigated the effects of opioids on the coexpressed mu-opioid (MOP) and nociceptin/orphanin FQ (NOP) receptors in human embryonic kidney (HEK) 293 cells. Our findings suggest that morphine, but not buprenorphine, facilitates the formation of MOP-NOP heterodimers and enhances their localization on lipid rafts. Moreover, morphine stimulates the phosphorylation of Erk1/2 in cells expressing MOP and MOP+NOP receptors, while buprenorphine appears to activate Erk1/2 solely through NOP receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Francesca Felicia Caputi, Serena Stopponi, Laura Rullo, Martina Palmisano, Massimo Ubaldi, Sanzio Candeletti, Roberto Ciccocioppo, Patrizia Romualdi
Summary: The genetically selected Marchigian Sardinian alcohol-preferring (msP) rats exhibit innate up-regulation of the CRF system for negative mood and stress responses, as well as inherent up-regulation of the N/OFQ system for anti-stress responses. Alcohol consumption dampens N/OFQ and results in a complex reorganization of neuropeptidergic systems in the extended amygdala of msP rats.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Salvatore Pacifico, Valentina Albanese, Davide Illuminati, Erika Marzola, Martina Fabbri, Federica Ferrari, Victor A. D. Holanda, Chiara Sturaro, Davide Malfacini, Chiara Ruzza, Claudio Trapella, Delia Preti, Ettore Lo Cascio, Alessandro Arcovito, Stefano Della Longa, Martina Marangoni, Davide Fattori, Romina Nassini, Girolamo Calo, Remo Guerrini
Summary: In this study, 31 peptides were synthesized and tested for their activity at human recombinant NOP/opioid receptors. The peptide [Dmt(1,5)]N/OFQ(1-13)-NH2 was identified as the most potent dual NOP/mu receptor agonist, with antitussive effects demonstrated in vivo. The molecular mechanisms of peptide binding to the mu receptor were elucidated through experimental and in silico studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Sarah Sayers, Nikki Le, Jennifer Hernandez, Veronica Mata-Pacheco, Edward J. Wagner
Summary: N/OFQ(ARC) neurons play a vital role in promoting rebound hyperphagia by inhibiting anorexigenic neural substrates under negative energy balance conditions, an effect that is diminished by E-2 in females.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Chemistry, Analytical
Raffaele Lecce, Luca Regazzoni, Carlo Mustazza, Giampaolo Incarnato, Rita Porra, Alessia Panusa
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2016)
Review
Biochemistry & Molecular Biology
Carlo Mustazza, Stefano Pieretti, Francesca Marzoli
CURRENT MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Anna Borioni, Giuditta Bastanzio, Maurizio Delfini, Carlo Mustazza, Fabio Sciubba, Massimo Tatti, Maria Rosaria Del Giudice
BIOORGANIC CHEMISTRY
(2011)
Article
Chemistry, Medicinal
Maria Rosaria Del Giudice, Anna Borioni, Giuditta Bastanzio, Maria Sbraccia, Carlo Mustazza, Isabella Sestili
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2011)
Article
Chemistry, Medicinal
Carlo Mustazza, Anna Borioni, Isabella Sestili, Maria Sbraccia, Andrea Rodomonte, Maria Rosaria Del Giudice
JOURNAL OF MEDICINAL CHEMISTRY
(2008)
Article
Chemistry, Analytical
Carlo Mustazza, Anna Borioni, Andrea Luca Rodomonte, Monica Bartolomei, Eleonora Antoniella, Piera Di Martino, Luisa Valvo, Isabella Sestili, Eliana Costantini, Maria Cristina Gaudiano
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2014)
Article
Biochemistry & Molecular Biology
Carlo Mustazza, Marco Sbriccoli, Anna Borioni, Rosella Ferretti, Maria Rosaria Del Giudice
Review
Biochemistry & Molecular Biology
Carlo Mustazza, Marco Sbriccoli, Paola Minosi, Carla Raggi
CURRENT MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Applied
Roberto Cirilli, Francesca Romana Gallo, Giuseppina Multari, Giovanna Palazzino, Carlo Mustazza, Alessia Panusa
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
(2020)
Article
Oncology
N. Calandrella, G. Risuleo, G. Scarsella, C. Mustazza, M. Castelli, F. Galati, A. Giuliani, G. Galati
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2007)
Article
Biochemical Research Methods
Fabiana Piccioni, Anna Borioni, Maurizio Delfini, Maria Rosaria Del Gludice, Carlo Mustazza, Andrea Rodornonte, Gianfranco Risuleo
ANALYTICAL BIOCHEMISTRY
(2007)
Article
Chemistry, Medicinal
Anna Borioni, Carlo Mustazza, Isabella Sestili, Maria Sbraccia, Luciana Turchetto, Maria Rosaria Del Giudice
ARCHIV DER PHARMAZIE
(2007)
Article
Chemistry, Medicinal
Carlo Mustazza, Anna Borioni, Isabella Sestili, Maria Sbraccia, Andrea Rodomonte, Rosella Ferretti, Maria Rosaria Del Giudice
CHEMICAL & PHARMACEUTICAL BULLETIN
(2006)
Article
Chemistry, Medicinal
I Sestili, A Borioni, C Mustazza, A Rodomonte, L Turchetto, M Sbraccia, D Riitano, MR Del Giudice
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2004)