Article
Biochemistry & Molecular Biology
Stefanie Kampen, David Rodriguez, Morten Jorgensen, Monika Kruszyk-Kujawa, Xinyan Huang, Michael Collins, Noel Boyle, Damien Maurel, Axel Rudling, Guillaume Lebon, Jens Carlsson
Summary: This study conducted molecular docking screens to identify allosteric modulators of the metabotropic glutamate receptor 5 (mGlu(5)). Four compounds with the highest affinities were confirmed to be negative allosteric modulators of mGlu(5) signaling.
ACS CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yingyi Zhang, Patricia M. Dijkman, Rongfeng Zou, Martina Zandl-Lang, Ricardo M. Sanchez, Luise Eckhardt-Strelau, Harald Kofeler, Horst Vogel, Shuguang Yuan, Mikhail Kudryashev
Summary: The study presents structures of the pLGIC 5-HT3A serotonin receptor reconstituted into lipid bilayer discs, showing lipid-protein interactions and asymmetric activation of the homopentameric receptor.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Alessandro Crnjar, Susanne M. Mesoy, Sarah C. R. Lummis, Carla Molteni
Summary: Pentameric ligand-gated ion channels (pLGICs) play a crucial role in fast synaptic transmission and are important drug targets. The M4 helix is key to channel opening, connecting radially through M1 to the hydrophobic gate on the pore-lining helix M2.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Pharmacology & Pharmacy
Gaia Pasqualetto, Marika Zuanon, Andrea Brancale, Mark T. Young
Summary: P2X receptors are ATP-gated cation channels that play key roles in nerve transmission, pain sensation, and inflammation. P2X4 receptor has attracted interest from pharmaceutical companies due to its roles in neuropathic pain and vascular tone modulation. A study confirmed the importance of a specific amino acid (I312T) for the sensitivity of the P2X4 receptor antagonist BX430 and identified a plausible binding pocket for a series of P2X4 antagonists.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Agronomy
Andrew K. Jones, Delphine Goven, Josy-Anne Froger, Alexandre Bantz, Valerie Raymond
Summary: The cysLGIC superfamilies of Blattella germanica and Periplaneta americana are the largest insect cysLGIC superfamilies characterized to date, with 30 and 32 subunit-encoding genes, respectively. These cockroaches possess ion channels predicted to be gated by acetylcholine, gamma-aminobutyric acid, glutamate, histamine, as well as orthologues of the drosophila pH-sensitive chloride channel (pHCl), CG8916 and CG12344. The diversity of the cockroach cysLGICs is broadened by alternative splicing and RNA A-to-I editing.
PEST MANAGEMENT SCIENCE
(2021)
Article
Chemistry, Medicinal
Jianping Chen, Erik J. Garcia, Christina R. Merritt, Joshua C. Zamora, Andrew A. Bolinger, Konrad Pazdrak, Susan J. Stafford, Randy C. Mifflin, Eric A. Wold, Christopher T. Wild, Haiying Chen, Noelle C. Anastasio, Kathryn A. Cunningham, Jia Zhou
Summary: In this study, novel oleamide analogues were designed and synthesized as selective 5-HT2CR agonists or dual 5-HT2CR/5-HT2AR positive allosteric modulators using a fragment-based discovery approach. Compound 13 (JPC0323) showed on-target properties, acceptable plasma exposure and brain penetration, and negligible displacement to orthosteric sites of over 50 GPCRs and transporters. Moreover, compound 13 suppressed novelty-induced locomotor activity in a 5-HT2CR-dependent manner, indicating 5-HT2CR agonist activity at the whole organism level at the employed doses of 13. This research discovered new selective 5-HT2CR agonists and first-in-class 5-HT2CR/5-HT2AR dual positive allosteric modulators, expanding the pharmacological toolbox for exploring the biology of these important receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
James S. Kimber, Joshua G. Kovoor, John M. Glynatsis, Samuel J. West, Thi Thien Nhi Mai, Jonathan Henry W. Jacobsen, Christopher D. Ovenden, Stephen Bacchi, Joseph N. Hewitt, Aashray K. Gupta, Suzanne Edwards, Fiona J. Taverner, David I. Watson
Summary: The purpose of this study was to compare isopropyl alcohol (IPA) with 5-HT3 antagonists for the treatment of nausea. Four randomized controlled trials (RCTs) with 382 participants were included. The results showed that IPA provided quicker and more effective relief of nausea compared to 5-HT3 antagonists.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Makoto Ihara
Summary: The Cys-loop superfamily of ligand-gated ion channels is widely present in vertebrates and invertebrates, serving as targets for various classes of pesticides. These pesticides have high target site selectivity, contributing to their safety in insecticide use. Structural analyses, particularly X-ray crystal structures, have revealed details of molecular interactions between insecticides and their targets, aiding in understanding the mechanisms of neuroactive insecticides targeting these ion channels.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Marie Lycksell, Urska Rovsnik, Anton Hanke, Anne Martel, Rebecca J. Howard, Erik Lindahl
Summary: This study characterized the structure and dynamics of DeCLIC using cryo-EM, SANS, and MD simulations, revealing alternative conformations of the NTD and calcium-binding site and expanding the conformational landscape of the pLGIC family. Moreover, it demonstrated the power of combining low-resolution scattering, high-resolution structural, and MD simulation data to elucidate highly conserved interfacial interactions in the pLGIC family.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Anesthesiology
Hyun-Jung Shin, Jiwon Yoon, Hyo-Seok Na
Summary: The study found that 5-HT3 receptor antagonists may significantly reduce the risk of POD in older patients undergoing orthopedic lower limb surgery, with palonosetron showing better preventive effects.
PERIOPERATIVE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Filip Koniuszewski, Florian D. Vogel, Konstantina Bampali, Jure Fabjan, Thomas Seidel, Petra Scholze, Philip B. Schmiedhofer, Thierry Langer, Margot Ernst
Summary: This study explores the potential for polypharmacology among pLGICs, revealing that ligands can interact with homologous sites in many members of the superfamily and multiple pockets in distinct localizations of individual receptor subtypes share common ligands. This poses challenges for the development of selective agents.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Santosh T. R. B. Rao, Ilona Turek, Julian Ratcliffe, Simone Beckham, Cassandra Cianciarulo, Siti S. B. M. Y. Adil, Christine Kettle, Donna R. Whelan, Helen R. Irving
Summary: This study investigated the distribution of 5-HT3 receptor subunits in intracellular and cell-free mitochondria. A and E subunits were found to be localized on the inner membrane of the mitochondria and could form heteromeric complexes. Cell-free mitochondria colocalized with the fluorescent signal for A subunits. The presence of A and E subunits affected changes in membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin, which were inhibited by pre-treatment with ondansetron. It is likely that the 5-HT3 receptors on mitochondria directly impact mitochondrial function and may have therapeutic implications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Angela Arsova, Thor C. Moller, Shane D. Hellyer, Line Vedel, Simon R. Foster, Jakob L. Hansen, Hans Brauner-Osborne, Karen J. Gregory
Summary: This study provides detailed characterization of the binding and functional pharmacological properties of three structurally diverse mGlu(5) PAMs and is the first assessment of the effects of PAMs on receptor internalization.
MOLECULAR PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ryan Gallagher, Taima Qudah, Thomas Balle, Mary Chebib, Malcolm D. McLeod
Summary: Analogues of methyllycaconitine (MLA) incorporating modified ester sidechains were designed and synthesized, showing selective non-competitive inhibition for specific nAChR subtypes. This study defines the biological effects of MLA analogues more clearly and identifies strategies for developing selective ligands for the alpha 4 beta 2 nAChR subtype.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Anesthesiology
Hyun-Jung Shin, Ji In Park, Sohyun Lee, Jung-Won Hwang, Hyo-Seok Na
Summary: This retrospective study investigated the association between 5-hydroxytryptamine 3 (5-HT3) receptor antagonists and postoperative delirium (POD) in older adults who underwent hip fracture surgery. The results indicated that the intraoperative use of 5-HT3 receptor antagonists can reduce the incidence of POD and can be considered as one of the preventive strategies for POD in older adults undergoing hip fracture surgery.
JOURNAL OF ANESTHESIA
(2023)
Article
Biochemistry & Molecular Biology
Linjing Mu, Adrienne Muller Herde, Pascal M. Ruefli, Filippo Sladojevich, Selena Milicevic Sephton, Stefanie D. Kramer, Andrew J. Thompson, Roger Schibli, Simon M. Ametamey, Martin Lochner
ACS CHEMICAL NEUROSCIENCE
(2016)
Article
Neurosciences
Marc-David Ruepp, Hao Wei, Michele Leuenberger, Martin Lochner, Andrew J. Thompson
Article
Neurosciences
Andrew J. Thompson, Simon Metzger, Martin Lochner, Marc-David Ruepp
Article
Biochemistry & Molecular Biology
Thomas Jack, Michele Leuenberger, Marc-David Ruepp, Sanjeev Kumar V. Vernekar, Andrew J. Thompson, Sophie Braga-Lagache, Manfred Heller, Martin Lochner
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Neurosciences
Paul Beswick, Ben Wahab, Mark A. Honey, Michael Paradowski, Ke Jiang, Martin Lochner, Ruth D. Murrell-Lagnado, Andrew J. Thompson
Article
Immunology
Agila Kumari Pragasam, Derek Pickard, Vanessa Wong, Gordon Dougan, Gagandeep Kang, Andrew Thompson, Jacob John, Veeraraghavan Balaji, Ankur Mutreja
CLINICAL INFECTIOUS DISEASES
(2020)
Article
Biochemistry & Molecular Biology
Samantha C. Salvage, Johanna S. Rees, Alexandra McStea, Michael Hirsch, Lin Wang, Christopher J. Tynan, Matthew W. Reed, Jennifer R. Irons, Richard Butler, Andrew J. Thompson, Marisa L. Martin-Fernandez, Christopher L-H Huang, Antony P. Jackson
Article
Multidisciplinary Sciences
Gavin E. Jarvis, Andrew J. Thompson
SCIENTIFIC REPORTS
(2019)
Article
Health Policy & Services
James O'Donovan, Andrew Thompson, Christina Stiles, Japheth A. Opintan, Ken Kabali, Ian Willis, Mwebe Edward Mutimba, Elizabeth Nalweyiso, Henry Mugabi, David P. Kateete, Matthew Ameniko, George Govina, Rachel Weberman, Edward O'Neil, Niall Winters, Ankur Mutreja
HEALTH PROMOTION INTERNATIONAL
(2020)
Article
Cell Biology
Maria L. Balmer, Eric H. Ma, Andrew J. Thompson, Raja Epple, Gunhild Unterstab, Jonas Loetscher, Philippe Dehio, Christian M. Schuerch, Jan D. Warncke, Gaelle Perrin, Anne-Kathrin Woischnig, Jasmin Graehlert, Jordan Loeliger, Nadine Assmann, Glenn R. Bantug, Olivier P. Schaeren, Nina Khanna, Adrian Egli, Lukas Bubendorf, Katharina Rentsch, Siegfried Hapfelmeier, Russell G. Jones, Christoph Hess
Article
Biochemistry & Molecular Biology
Andrew J. Thompson, Paul S. Verdin, Mark J. Burton, T. G. Emyr Davies, Martin S. Williamson, Linda M. Field, Richard A. Baines, Ian R. Mellor, Ian R. Duce
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Chemistry, Physical
K-T Lam, E. L. Taylor, A. J. Thompson, M-D Ruepp, M. Lochner, Michael J. Martinez, J. A. Brozik
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Review
Public, Environmental & Occupational Health
James O'Donovan, Andrew Thompson, Chinelo Onyilofor, Taylor Hand, Natalie Rosseau, Edward O'Neil
GLOBAL PUBLIC HEALTH
(2019)
Review
Pharmacology & Pharmacy
Samantha C. Salvage, Karthik H. Chandrasekharan, Kamalan Jeevaratnam, Angela F. Dulhunty, Andrew J. Thompson, Antony P. Jackson, Christopher L-H Huang
BRITISH JOURNAL OF PHARMACOLOGY
(2018)
Article
Pharmacology & Pharmacy
Gavin E. Jarvis, Roseli Barbosa, Andrew J. Thompson
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2016)