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
Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System.
Kurt F. Hauser,Pamela E. Knapp +1 more
TL;DR: This article surveys prior studies on the effects of opiates on CNS maturation, and suggests new directions for future research in this area, including identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure during maturation.
Journal ArticleDOI
Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective.
TL;DR: It is proposed that targeting mu opioid receptor heterodimers may represent an opportunity to develop new therapeutics, especially for chronic pain treatment.
Journal ArticleDOI
Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling.
Alexander Samoshkin,Marino Convertino,Chi T. Viet,Jeffrey S. Wieskopf,Oleg Kambur,Jaclyn Marcovitz,Pinkal Patel,Laura S. Stone,Eija Kalso,Jeffrey S. Mogil,Brian L. Schmidt,William Maixner,Nikolay V. Dokholyan,Luda Diatchenko +13 more
TL;DR: Evidence is provided that the heterodimerization of 6TM-MOR with β2-AR underlies a molecular mechanism for 6TM cellular signaling, presenting a unique functional responses to opioids, providing a new avenue for opioid therapy.
Journal ArticleDOI
Simultaneous Activation of Mu and Delta Opioid Receptors Reduces Allodynia and Astrocytic Connexin 43 in an Animal Model of Neuropathic Pain.
Nunzio Vicario,Lorella Pasquinucci,Federica M. Spitale,Santina Chiechio,Rita Turnaturi,Filippo Caraci,Daniele Tibullo,Roberto Avola,Rosario Gulino,Rosalba Parenti,Carmela Parenti +10 more
TL;DR: The effects of the benzomorphan ligand LP2, a multitarget MOR/DOR agonist, in an experimental model of neuropathic pain induced by the unilateral sciatic nerve chronic constriction injury on male Sprague-Dawley rats showed that LP2 significantly ameliorated mechanical allodynia from the early phase of treatment up to 21 days post-ligatures.
Journal ArticleDOI
Natural Products for the Treatment of Pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide.
TL;DR: The natural products salvinorin A, mitragynine and collybolide represent three non-morphinan natural product-based targets which are potent selective agonists of opioid receptors, and emerging next-generation analgesics.
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