Review
Pharmacology & Pharmacy
Jordan T. Bateman, Sandy E. Saunders, Erica S. Levitt
Summary: This review aims to provide a comprehensive understanding of the pharmacological mechanisms of opioid-induced respiratory depression, with the goal of improving therapeutic options for opioid overdose and other detrimental effects on breathing. The review discusses the development of tolerance in the respiratory system and differences in the degree of respiratory depression caused by different opioid agonists. Potential future therapeutic agents targeting non-opioid receptors are also explored.
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
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
Neurosciences
Jennifer M. Bossert, Carlos A. Mejias-Aponte, Thomas Saunders, Lindsay Altidor, Michael Emery, Ida Fredriksson, Ashley Batista, Sarah M. Claypool, Kiera E. Caldwell, David J. Reiner, Jonathan J. Chow, Matthew Foltz, Vivek Kumar, Audrey Seasholtz, Elizabeth Hughes, Wanda Filipiak, Brandon K. Harvey, Christopher T. Richie, Francois Vautier, Juan L. Gomez, Michael Michaelides, Brigitte L. Kieffer, Stanley J. Watson, Huda Akil, Yavin Shaham
Summary: By introducing the Oprm1-Cre knock-in transgenic rat, this study investigated the role of the mu-opioid receptor (MOR) in heroin self-administration. The study found that heroin self-administration showed different patterns in male and female Oprm1-Cre rats. This research provides new strategies for understanding the involvement of MOR-expressing cells in opioid addiction, pain-related behaviors, and other opioid-mediated functions.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
David De Sa Nogueira, Romain Bourdy, Dominique Filliol, Pascal Romieu, Katia Befort
Summary: This study investigated transcriptional and functional changes of the mu opioid receptor in reward-related brain regions induced by intravenous cocaine self-administration in rats. The findings revealed increased mu opioid receptor gene expression and enhanced functionality in the hippocampus of cocaine self-administering animals. The study highlights the hippocampus as an important target for further investigation of neuroadaptive processes leading to cocaine addiction.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Nikolas Bergum, Casey-Tyler Berezin, Connie M. King, Jozsef Vigh
Summary: Opioid drugs are effective for treating moderate to severe pain, but long-term use can lead to tolerance, addiction, and sleep/wake disturbances. This study suggests that intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing mu-opioid receptors (MORs) may contribute to opioid-related sleep/wake problems and thermoregulatory changes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Shijia Liu, Dong-Il Kim, Tae Gyu Oh, Gerald M. Pao, Jong-Hyun Kim, Richard D. Palmiter, Matthew R. Banghart, Kuo-Fen Lee, Ronald M. Evans, Sung Han
Summary: Neurons expressing the mu-opioid receptor within the lateral parabrachial nucleus play a crucial role in opioid-induced respiratory depression (OIRD). Chemogenetic modulation of these neurons can rescue respiratory rhythms and serve as a potential therapeutic target for treating OIRD in patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Stevenson Desmercieres, Virginie Lardeux, Jean-Emmanuel Longueville, Myriam Hanna, Leigh Panlilio, Nathalie Thiriet, Marcello Solinas
Summary: The newly developed PSS procedure provides a quantifiable breakpoint to measure animals' propensity to continue working for a reward despite progressively increasing electric shock intensity. The break point is sensitive to hunger and changes in the qualitative incentive value of the reward, and it shows differences compared to the traditional PR procedure.
Article
Neurosciences
Megan J. Moerke, S. Stevens Negus
Summary: The study aimed to examine the time parameters of enhanced opioid reward after initial opioid exposure. Results showed that the enhanced opioid reward was relatively transient, but could be produced by a range of different dosing frequencies.
PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Cassandra L. Retzlaff, Patrick E. Rothwell
Summary: This study is the first to examine the physiological properties of neuropeptide Y interneurons in the nucleus accumbens and shows that activation of mu opioid receptors inhibits the activity of low-threshold spiking interneurons and reduces GABA release onto medium spiny neurons.
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
Neurosciences
Nicole E. Ochandarena, Jesse K. Niehaus, Adrien Tassou, Gregory Scherrer
Summary: Opioids are effective analgesics used for pain management, but they have dangerous side effects such as addiction and respiratory depression. The prevalence of opioid abuse and overdose deaths has created an urgent need for safer pain medications and treatments for opioid use disorders. Understanding the cell types and neural circuits responsible for the analgesic and addictive properties of opioids is crucial for research. Single-cell RNA sequencing technology has allowed the identification of MOR-expressing cell types and offers new opportunities for mapping opioid effects onto these cell types.
Article
Neurosciences
Jin Bai, Ting Ye, Yan-bin Wei, Yi Yang, He-min Yang, Yan Lan
Summary: Opioid receptors play important roles in regulating synaptic transmission in the cerebellum, especially at the parallel fiber-Purkinje cell synapses. Activation of mu-opioid receptors and 6-opioid receptors inhibits glutamate release and modulates synaptic transmission, while no significant effects were observed with x-opioid receptor activation. Endogenous opioid peptides also contribute to the modulation of synaptic transmission at these synapses.
NEUROSCIENCE LETTERS
(2022)
Article
Chemistry, Medicinal
Taryn Bosquez-Berger, Jessica A. Gudorf, Charles P. Kuntz, Jacob A. Desmond, Jonathan P. Schlebach, Michael S. VanNieuwenhze, Alex Straiker
Summary: The US is facing a severe increase in fatal drug overdoses, with synthetic opioids like fentanyl causing 80% of deaths. Naloxone, the only antidote for opiate overdose, struggles against these synthetic opioids. A study has found that (-)-Cannabidiol ((-)-CBD), a candidate negative allosteric modulator (NAM) for the mu opioid receptor, shows potential as a more potent NAM than naloxone. The study suggests that CBD analogs have potential for the development of next-generation antidotes for opioid overdose.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Neurosciences
Kyle A. Windisch, Michelle Morochnik, Brian Reed, Mary Jeanne Kreek
Summary: The mu opioid receptor antagonist/kappa opioid receptor (KOR) partial agonist nalmefene (NMF) did not significantly reduce cocaine intake, but acute pretreatment of 1 mg/kg NMF significantly potentiated cocaine motivation. Further research with KOR selective partial or full agonists is required to determine their effect on cocaine reinforcement.