Article
Biochemistry & Molecular Biology
Soichiro Ide, Noriaki Iwase, Kenichi Arai, Masahiro Kojima, Shigeru Ushiyama, Kaori Taniko, Kazutaka Ikeda
Summary: Despite the widespread use of opioids for pain management, opioid addiction and the overdose crisis are becoming increasingly serious. A new nonpeptide ligand, UD-030, has been found to be a selective mu-opioid receptor antagonist and shows promise as a treatment option for opioid use disorder, with different characteristics from traditional medications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Keith M. Olson, Andrea L. Devereaux, Payal Chatterjee, Savanah L. Saldana-Shumaker, Amanda Shafer, Adam Plotkin, Ram Kandasamy, Alexander D. MacKerell, John R. Traynor, Christopher W. Cunningham
Summary: This study investigates the structure-activity relationships of benzylideneoxymorphone analogs in order to develop analgesics with reduced tolerance and side effects. One compound, nitro-BOM (NBOM), showed high-efficacy antinociception but also exhibited tolerance and toxicity upon repeated administration. Despite these issues, NBOM provides an important tool for understanding MOPr/DOPr pharmacology.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zachary W. Reichenbach, Kelly DiMattio, Suren Rajakaruna, David Ambrose, William D. Cornwell, Ronald J. Tallarida, Thomas Rogers, Lee-Yuan Liu-Chen, Ronald F. Tuma, Sara Jane Ward
Summary: Non-selective cannabinoid (CB) agonists can enhance the analgesic effects of morphine but inhibit its antinociceptive tolerance. Activation of CB2 receptors can reverse allodynia and hyperalgesia in chronic pain models, and co-administration of CB2 receptor selective agonists with morphine can synergistically enhance the effects. However, the interactions between CB2 receptor selective agonist O-1966 and morphine depend on the order of administration.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Madeline R. Hennessy, Anna M. Gutridge, Alexander R. French, Elizabeth S. Rhoda, Yazan J. Meqbil, Meghna Gill, Yavnika Kashyap, Kevin Appourchaux, Barnali Paul, Zaijie Jim Wang, Richard M. van Rijn, Andrew P. Riley
Summary: Akuammine and pseudoakuammigine are indole alkaloids derived from the seeds of the akuamma tree. They act as weak agonists of the mu opioid receptor and show minimal effects in animal models of antinociception. By synthesizing 22 semisynthetic derivatives and evaluating their activity at the mu opioid receptor and kappa opioid receptor, we identified derivatives with improved potency at the mu opioid receptor.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Vishakh Iyer, Claudia Rangel-Barajas, Taylor J. Woodward, Abhijit Kulkarni, Lucas Cantwell, Jonathon D. Crystal, Ken Mackie, George V. Rebec, Ganesh A. Thakur, Andrea G. Hohmann
Summary: Researchers have developed a novel drug candidate that can block the rewarding effects of opioid drugs by attenuating the signaling of cannabinoid type 1 (CB1) receptors. This drug works by decreasing the affinity and/or efficacy of CB1 ligands. The results show that this drug could potentially be used to prevent opioid reward and treat opioid abuse without unwanted side effects.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Psychiatry
Javier Ballester, Anne K. Baker, Ilkka K. Martikainen, Vincent Koppelmans, Jon-Kar Zubieta, Tiffany M. Love
Summary: This study found that chronic pain patients at high risk for opioid misuse showed higher baseline MOR availability in the right amygdala, while patients at low risk for opioid misuse showed less pain-induced activation of MOR-mediated, endogenous opioid neurotransmission in the nucleus accumbens.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Neurosciences
Julia E. R. Nickols, Serdar M. Dursun, Anna M. W. Taylor
Summary: Opioid addiction is characterized by changes in the dopamine system, and the use of dopamine partial agonists like brexpiprazole may help restore dopamine signaling during drug withdrawal. In a mouse model, brexpiprazole treatment was found to attenuate locomotor sensitization, abolish morphine place preference, and prevent the expression of opioid-induced hyperalgesia.
Article
Clinical Neurology
Ariadna Requana Aradas, Youssra Djaboub, Isabelle McCort-Tranchepain, Zuzana Hajasova, Loic Clemenceau, Corinne Canestrelli, Anika Mann, Stefan Schulz, Angelique Delaval, Francine Acher, Dominique Massotte, Florence Noble, Nicolas Marie
Summary: Evidence suggests that targeting opioid receptor heteromers may reduce side effects of opioid drugs while maintaining therapeutic effects. This study examined the effects of CYM51010, a MOR-DOR heteromer-preferring agonist, in mouse models of drug addiction, and found that it had similar effects to morphine in some aspects but induced less physical dependence. The results indicate that targeting MOR-DOR heteromers could be a promising strategy to block morphine reward.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Cell Biology
Kateryna Murlanova, Yan Jouroukhin, Ksenia Novototskaya-Vlasova, Shovgi Huseynov, Olga Pletnikova, Michael J. J. Morales, Yun Guan, Atsushi Kamiya, Dwight E. E. Bergles, David M. M. Dietz, Mikhail V. V. Pletnikov
Summary: The function of mu opioid receptors in astrocytes and their role in reward- and aversion-associated behaviors have been investigated. The knockout of mu opioid receptors in astrocytes did not affect locomotor activity, anxiety, or object recognition in mice exposed to morphine. However, it enhanced locomotor activity and conditioned place aversion during naloxone-precipitated morphine withdrawal, which lasted for up to 6 weeks.
Article
Pharmacology & Pharmacy
Marc Lopez-Cano, Joan Font, Ester Aso, Kristoffer Sahlholm, Gisela Cabre, Jesus Giraldo, Yves De Koninck, Jordi Hernando, Amadeu Llebaria, Victor Fernandez-Duenas, Francisco Ciruela
Summary: Photopharmacology offers a promising approach to improve the benefit/risk profiles of opioid-based drugs. This study successfully developed a morphine photo-derivative that can be activated by light, providing effective analgesia without the occurrence of tolerance or associated opioid-related side effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Jia-Jia Zhang, Chang-Geng Song, Miao Wang, Gai-Qin Zhang, Bin Wang, Xi Chen, Peng Lin, Yu-Meng Zhu, Zhi-Chuan Sun, Ya-Zhou Wang, Jian-Li Jiang, Ling Li, Xiang-Min Yang, Zhi-Nan Chen
Summary: In this study, a monoclonal antibody 3A5C7 targeting MOR was developed to alleviate morphine tolerance and dependence by enhancing morphine-induced MOR endocytosis. This provides promising translational value for clinical treatment of morphine tolerance.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2023)
Article
Pharmacology & Pharmacy
Anna M. Gutridge, Soumen Chakraborty, Balazs R. Varga, Elizabeth S. Rhoda, Alexander R. French, Arryn T. Blaine, Quinten H. Royer, Haoyue Cui, Jinling Yuan, Robert J. Cassell, Mark Szabo, Susruta Majumdar, Richard M. van Rijn
Summary: Kratom alkaloids such as paynantheine and speciogynine have the potential to be used in developing novel opioid drugs for the treatment of alcohol use disorder, as they reduce alcohol consumption in mice and show effects in behavioral experiments without causing significant euphoria.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Josue Jaramillo-Polanco, Cintya Lopez-Lopez, Yang Yu, Emma Neary, Alan Hegron, Meritxell Canals, Nigel W. Bunnett, David E. Reed, Alan E. Lomax, Stephen J. Vanner
Summary: This study found that chronic high-dose opioid exposure leads to opioid-induced hyperalgesia (OIH) in the gastrointestinal tract, which is mediated by DOPr signaling and dependent on receptor endocytosis and protein kinase C signaling.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Ying-Ting Hsu, Shen-Ren Chen, Yung-Chiao Chang, Hsiao-Fu Chang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Hsing-Pang Hsieh, Shau-Hua Ueng, Shiu-Hwa Yeh
Summary: The demand for a non-addictive analgesic medication is increasing due to clinical misuse. Compound 14 is a dual agonist of the mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor, providing pain relief at very small doses and reducing unwanted side effects. Evaluating its effects in wild type and humanized mice can help develop a safer prescription analgesic drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Licet Caridad Mena-Valdes, Yisel Blanco-Hernandez, Josue Vidal Espinosa-Juarez, Francisco Javier Lopez-Munoz
Summary: The study demonstrated that in a neuropathic pain model, haloperidol enhanced the analgesic effect of morphine, delayed the development of morphine tolerance, and did not show significant adverse effects.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)