Mu Opioids and Their Receptors: Evolution of a Concept
Reads0
Chats0
TLDR
Understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years, which now reveals a complexity of the morphine- like agents andtheir receptors that had not been previously appreciated.Abstract:
Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated.read more
Citations
More filters
Journal ArticleDOI
A Structure-Activity Relationship Comparison of Imidazodiazepines Binding at Kappa, Mu, and Delta Opioid Receptors and the GABAA Receptor.
Guanguan Li,Amanda N. Nieman,Yeunus Mian,Nicolas M Zahn,Brandon N Mikulsky,Michael M Poe,Kashi Reddy Methuku,Yongfeng Liu,James M. Cook,Douglas C. Stafford,Leggy A. Arnold +10 more
TL;DR: It can be concluded that a subset of imidazodiazepines represents novel KOR ligands with high selectivity among opioid receptors.
Journal ArticleDOI
An Iterative O-Methyltransferase Catalyzes 1,11-Dimethylation of Aspergillus fumigatus Fumaric Acid Amides.
Daniel Kalb,Thorsten Heinekamp,Sebastian Schieferdecker,Markus Nett,Axel A. Brakhage,Dirk Hoffmeister +5 more
TL;DR: This work investigates the previously uncharacterized Aspergillus fumigatus methyltransferase FTPM, which is encoded next to the bimodular fumaric acid amide synthetase FtpA, and expects this work will help to identify and annotate natural product biosynthesis genes in various species.
Journal ArticleDOI
Emerging Role of Fentanyl in Antiplatelet Therapy.
TL;DR: The issue of fentanyl interactions with antiplatelet drugs is tackled, indicating that it may impair the action of ticagrelor: an oral P2Y12 receptor inhibitor acting as an antiplatelets drug.
Journal ArticleDOI
The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies
TL;DR: Recent drug-development efforts targeting KOR are highlighted, including the development of G-protein–biased ligands, mixed opioid agonists, and peripherally restricted ligands to reduce side-effects.
Journal ArticleDOI
Mapping the naloxone binding sites on the mu-opioid receptor using cell-based photocrosslinkers.
TL;DR: Results indicate that MOR has two naloxone binding sites and that the hydrophobic and polar/uncharged residues within these sites are important for nalxone binding.
References
More filters
Journal ArticleDOI
A Map of Human Genome Variation From Population-Scale Sequencing
Gonçalo R. Abecasis,David Altshuler,David Altshuler,Adam Auton,Lisa D Brooks,Richard Durbin,Richard A. Gibbs,Matthew E. Hurles,Gil McVean +8 more
TL;DR: The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype as mentioned in this paper, and the results of the pilot phase of the project, designed to develop and compare different strategies for genomewide sequencing with high-throughput platforms.
Journal ArticleDOI
Table S2: Trans-factors and trinucleotide repeat instability Trans-factor
Journal ArticleDOI
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Krzysztof Palczewski,Takashi Kumasaka,Tetsuya Hori,Craig A. Behnke,H. Motoshima,Brian A. Fox,I. Le Trong,David C. Teller,Tetsuji Okada,Ronald E. Stenkamp,Masaki Yamamoto,Masashi Miyano +11 more
TL;DR: This article determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution and found that the highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the sevenhelix transmembrane motif.
Book
Goodman & Gilman's The Pharmacological Basis of Therapeutics
TL;DR: Goodman and Gilman's the pharmacological basis of therapeutics , Goodman and Gilmann's the pharmaceutica basis for drug discovery, and more.
Journal ArticleDOI
Identification of two related pentapeptides from the brain with potent opiate agonist activity
John J. Hughes,T. W. Smith,H. W. Kosterlitz,Linda A. Fothergill,B. A. Morgan,Howard R. Morris +5 more
TL;DR: The evidence is based on the determination of the amino acid sequence of natural enkephalin by the dansyl–Edman procedure and by mass spectrometry followed by synthesis and comparison of the natural and synthetic peptides.
Related Papers (5)
Structural insights into µ-opioid receptor activation
Weijiao Huang,Aashish Manglik,AJ Venkatakrishnan,Toon Laeremans,Evan N. Feinberg,Adrian L. Sanborn,Hideaki E. Kato,Kathryn E. Livingston,Thor S. Thorsen,Ralf C. Kling,Sébastien Granier,Peter Gmeiner,Stephen M. Husbands,John R. Traynor,William I. Weis,Jan Steyaert,Ron O. Dror,Brian K. Kobilka +17 more
Structure-based discovery of opioid analgesics with reduced side effects
Aashish Manglik,Henry Lin,Dipendra K. Aryal,John D. McCorvy,Daniela Dengler,Gregory Corder,Anat Levit,Ralf C. Kling,Ralf C. Kling,Viachaslau Bernat,Harald Hübner,Xi Ping Huang,Maria F. Sassano,Patrick M. Giguère,Stefan Löber,Da Duan,Grégory Scherrer,Brian K. Kobilka,Peter Gmeiner,Bryan L. Roth,Brian K. Shoichet +20 more