Article
Biochemistry & Molecular Biology
Kristina Puls, Helmut Schmidhammer, Gerhard Wolber, Mariana Spetea
Summary: This study comprehensively evaluated the binding and activity of the peripheral opioid analgesic HS-731 at all opioid receptors using in silico methods. The results provide insights into the interaction patterns of HS-731 with the opioid receptors, highlighting the importance of specific amino acid residues for recognition and partial agonism. Additionally, experimental evidence showed the absence of affinity of HS-731 to the NOP receptor, with a specific amino acid residue preventing binding to the orthosteric binding pocket.
Article
Chemistry, Multidisciplinary
Ranit Lahmy, Harald Hubner, Maximilian F. Schmidt, Daniel Lachmann, Peter Gmeiner, Burkhard Konig
Summary: This study developed photoswitchable ligands that can activate or deactivate clinically relevant mu-opioid receptors using light, allowing for spatial and temporal control of biological activity in various biological investigations. These ligands, modeled after the known agonist fentanyl, can change geometry upon exposure to light and have different photophysical and biochemical properties, which could be valuable in further studying the functional significance of the mu-opioid receptor.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Arjun Muralidharan, Alexander Samoshkin, Marino Convertino, Marjo Hannele Piltonen, Pavel Gris, Jian Wang, Changyu Jiang, Richard Klares, Alexander Linton, Ru-Rong Ji, William Maixner, Nikolay V. Dokholyan, Jeffrey S. Mogil, Luda Diatchenko
Summary: This study developed compounds selective for 6TM- or 7TM-mu receptors through virtual screening and experimental validation, demonstrating their potential analgesic effects and serving as valuable research tools for the development of novel analgesics.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Siavash Shahbazi Nia, Mohammad Anwar Hossain, Guangchen Ji, Sravan K. Jonnalagadda, Samuel Obeng, Md Ashrafur Rahman, Ali Ehsan Sifat, Saeideh Nozohouri, Collin Blackwell, Dhavalkumar Patel, Jon Thompson, Scott Runyon, Takato Hiranita, Christopher R. McCurdy, Lance McMahon, Thomas J. Abbruscato, Paul C. Trippier, Volker Neugebauer, Nadezhda A. German
Summary: Based on the structure of gliotoxin, two chemotypes with selective affinity to the kappa opioid receptor (KOR) were synthesized. Through medicinal chemistry and structure-activity relationship (SAR) studies, the required structural features for high affinity were identified, and advanced molecules with favorable properties were prepared. Compound 2 was shown to block the pain-relieving effect of a KOR agonist both in vitro and in vivo, indicating its potential application as a pain therapeutic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Yui Kuroda, Miki Nonaka, Yuji Kamikubo, Haruo Ogawa, Takashi Murayama, Nagomi Kurebayashi, Hakushun Sakairi, Kanako Miyano, Akane Komatsu, Tetsushi Dodo, Kyoko Nakano-Ito, Keisuke Yamaguchi, Takashi Sakurai, Masako Iseki, Masakazu Hayashida, Yasuhito Uezono
Summary: The research found that the endothelin A receptor may affect pain mechanisms by heterodimerization with the mu opioid receptor, and the ETAR antagonist Compound-E can enhance the analgesic effects of morphine. These findings provide a new approach to reducing opioid use.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Neurosciences
Lihua Sun, Jing Tang, Heidi Liljenback, Aake Honkaniemi, Jenni Virta, Janne Isojarvi, Tomi Karjalainen, Tatu Kantonen, Pirjo Nuutila, Jarmo Hietala, Valtteri Kaasinen, Kari Kalliokoski, Jussi Hirvonen, Harry Scheinin, Semi Helin, Kim Eerola, Eriika Savontaus, Emrah Yatkin, Juha O. Rinne, Anne Roivainen, Lauri Nummenmaa
Summary: The study found that both humans and rats exhibit significant seasonal variations in cerebral MOR availability, primarily associated with seasonal changes in photoperiod. Changes in daylength were shown to influence MOR availability in the brain, impacting behaviors and physiological responses.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Xiaojing Cong, Damien Maurel, Helene Demene, Ieva Vasiliauskaite-Brooks, Joanna Hagelberger, Fanny Peysson, Julie Saint-Paul, Jerome Golebiowski, Sebastien Granier, Remy Sounier
Summary: GPCR functional selectivity presents new opportunities for designing safer drugs. Through a combination of functional assays, solution NMR spectroscopy, and molecular dynamic simulations, our study has identified specific mu OR conformations induced by G protein-biased agonists, shedding light on the dynamic mechanism enabling opioid ligands to preferentially activate the G protein pathway.
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
Biology
Seksiri Arttamangkul, Emily J. Platt, James Carroll, David Farrens
Summary: The study found that single cholinergic neurons in the mouse striatum express both MORs and DORs, and through fluorescent labeling and selective activation experiments, it was revealed their mechanisms in regulating cellular electrical activity. The results indicate that the two receptors function independently.
Article
Biochemistry & Molecular Biology
Sebastian Fritzwanker, Stefan Schulz, Andrea Kliewer
Summary: Opioid-associated respiratory depression overdoses and deaths are a major public health problem in the US and other Western countries. Research has focused on developing G-protein-biased mu-opioid receptor agonists to address this issue. Detailed analysis of receptor phosphorylation may provide novel insights into the pharmacological properties of newly synthesized MOP ligands.
Review
Chemistry, Medicinal
Tao Zhuang, Jiaying Xiong, Shuaishuai Hao, Wei Du, Zhenming Liu, Bifeng Liu, Guisen Zhang, Yin Chen
Summary: Opioid analgesics are effective for pain management but have undesirable side effects, prompting the need for new, safer analgesics. The sigma-1 receptor plays a crucial role in pain modulation and its antagonists can reduce pain and enhance the effects of opioid analgesics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mengkang Gao, Yang Zhang, Bingxin Wang, Ning Guo, Lulian Shao, Weibin Zhai, Lei Jiang, Qiang Wang, Hai Qian, Lin Yan
Summary: Currently, it is challenging to develop effective analgesic drugs with minimal side effects. Multi-target drug treatments have shown higher efficacy and fewer side effects compared to single-target drug therapies. In this study, novel MOR/TRPV1 dual active ligands were designed and synthesized, demonstrating the potential for simultaneous targeting of both MOR and TRPV1 with a single molecule in order to discover new analgesic treatments.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mariel M. Cardenas, Mirza A. Saputra, Deane A. Gordon, Andrea N. Sanchez, Nobuyuki Yamamoto, Jeffrey L. Gustafson
Summary: In this study, we reported the catalytic atroposelective syntheses of pharmaceutically relevant 3-arylquinolines through SNAr reactions mediated by Cinchona alkaloid-derived ureas. These reactions exhibited a range of dynamic kinetic resolution (DKR) and kinetic resolution (KR) characteristics, with different pathways depending on the stereochemical stability of the starting material. Furthermore, functionalization of the atropisomerically enriched quinolines into pharmaceutically privileged scaffolds was achieved with minimal observed racemization.
CHEMICAL COMMUNICATIONS
(2021)
Article
Neurosciences
Feng Du, Guangjuan Yin, Lei Han, Xi Liu, Dong Dong, Kaifang Duan, Jiantao Huo, Yanyan Sun, Longzhen Cheng
Summary: Chronic use of opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. In this study, researchers found that the loss of peripheral mu-opioid receptors (MORs) did not affect morphine-induced mechanical allodynia and anti-allodynic tolerance, suggesting that the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
NEUROSCIENCE BULLETIN
(2023)
Article
Toxicology
Marie H. Deventer, Mattias Persson, Antonio Laus, Eline Pottie, Annelies Cannaert, Graziella Tocco, Henrik Green, Christophe P. Stove
Summary: This study investigates the mu opioid receptor (MOR) activation potential of psychedelics with the NBOMe structure. The findings show that some NBOMe substances can activate MOR, and they may occupy the same binding pocket as conventional opioids. This discovery is important for understanding the pharmacological effects of new psychoactive substances.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Abhijeet Kapoor, Alex Travesset
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2015)
Article
Biochemistry & Molecular Biology
Sheetal Uppal, Amit Kumar Singh, Richa Arya, Debanjan Tewari, Neha Jaiswal, Abhijeet Kapoor, Amal Kanti Bera, Alo Nag, Suman Kundu
Article
Biochemistry & Molecular Biology
Nitika Mukhi, Sonali Dhindwal, Sheetal Uppal, Abhijeet Kapoor, Richa Arya, Pravindra Kumar, Jagreet Kaur, Suman Kundu
Article
Chemistry, Multidisciplinary
Andrew C. Kruegel, Madalee M. Gassaway, Abhijeet Kapoor, Andras Varadi, Susruta Majumdar, Marta Filizola, Jonathan A. Javitch, Dalibor Sames
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2016)
Article
Biochemistry & Molecular Biology
Jonathan H. Wardman, Ivone Gomes, Erin N. Bobeck, Jennifer A. Stockert, Abhijeet Kapoor, Paola Bisignano, Achla Gupta, Mihaly Mezei, Sanjai Kumar, Marta Filizola, Lakshmi A. Devi
Article
Biochemistry & Molecular Biology
Jonathan H. Wardman, Ivone Gomes, Erin N. Bobeck, Jennifer A. Stockert, Abhijeet Kapoor, Paola Bisignano, Achla Gupta, Mihaly Mezei, Sanjai Kumar, Marta Filizola, Lakshmi A. Devi
Article
Biochemistry & Molecular Biology
Taylor E. T. Hughes, David T. Lodowski, Kevin W. Huynh, Aysenur Yazici, John Del Rosario, Abhijeet Kapoor, Sandip Basak, Amrita Samanta, Xu Han, Sudha Chakrapani, Z. Hong Zhou, Marta Filizola, Tibor Rohacs, Seungil Han, Vera Y. Moiseenkova-Bell
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Taylor E. T. Hughes, David T. Lodowski, Kevin W. Huynh, Aysenur Yazici, John Del Rosario, Abhijeet Kapoor, Sandip Basak, Amrita Samanta, Xu Han, Sudha Chakrapani, Z. Hong Zhou, Marta Filizola, Tibor Rohacs, Seungil Han, Vera Y. Moiseenkova-Bell
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Sandip Basak, Yvonne Gicheru, Abhijeet Kapoor, Megan L. Mayer, Marta Filizola, Sudha Chakrapani
NATURE COMMUNICATIONS
(2019)
Article
Biology
Taylor E. T. Hughes, John Smith Del Rosario, Abhijeet Kapoor, Aysenur Torun Yazici, Yevgen Yudin, Edwin C. Fluck, Marta Filizola, Tibor Rohacs, Vera Y. Moiseenkova-Bell
Article
Pharmacology & Pharmacy
Abhijeet Kapoor, Davide Provasi, Marta Filizola
MOLECULAR PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Yuchen Zhou, Steven Ramsey, Davide Provasi, Amal El Daibani, Kevin Appourchaux, Soumen Chakraborty, Abhijeet Kapoor, Tao Che, Susruta Majumdar, Marta Filizola
Summary: Research on kratom, a natural alternative for pain management, has intensified due to mounting reports of individuals finding pain relief with this product. Three alkaloids found in kratom, mitragynine, 7-hydroxymitragynine, and mitragynine pseudoindoxyl, have shown potential for pain relief with limited side effects. These alkaloids have been shown to selectively activate the G protein signaling pathway by binding and modulating the mu-opioid receptor, providing insight for the design of improved therapeutics.
Article
Neurosciences
Kerri D. Pryce, Hye Jin Kang, Farhana Sakloth, Yongfeng Liu, Susan Khan, Katalin Toth, Abhijeet Kapoor, Andrew Nicolais, Tao Che, Lihuai Qin, Feodora Bertherat, H. Umit Kaniskan, Jian Jin, Michael D. Cameron, Bryan L. Roth, Venetia Zachariou, Marta Filizola
Summary: The study found that two MOR PAMs molecules can maximize the analgesic effects of opioid drugs while reducing adverse reactions and overdose risks. These molecules show efficacy in mouse pain models and do not enhance adverse reactions associated with opioid drugs.
Article
Biology
Sandip Basak, Arvind Kumar, Steven Ramsey, Eric Gibbs, Abhijeet Kapoor, Marta Filizola, Sudha Chakrapani