Mu Opioids and Their Receptors: Evolution of a Concept
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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
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Usefulness of knockout mice to clarify the role of the opioid system in chronic pain
TL;DR: The novel genetic tools now available to manipulate specific neuronal populations and precise genome editing in mice will facilitate in a near future the elucidation of the role of each component of the endogenous opioid system in chronic pain.
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Truncated μ-Opioid Receptors With 6 Transmembrane Domains Are Essential for Opioid Analgesia.
Zhigang Lu,Jin Xu,Mingming Xu,Grace C. Rossi,Susruta Majumdar,Gavril W. Pasternak,Ying-Xian Pan +6 more
TL;DR: The study demonstrated the pharmacological relevance of mouse 6TM variants in IBNtxA analgesia and established that a common functional core of the receptors corresponding to the transmembrane domains encoded by exons 2 and 3 is sufficient for activity.
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A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects
Soumen Chakraborty,Jeffrey F. DiBerto,Abdelfattah Faouzi,Sarah M Bernhard,Anna M. Gutridge,Steven Ramsey,Yuchen Zhou,Davide Provasi,Nitin Nuthikattu,Rahul Jilakara,Melissa Nelson,Wesley B. Asher,Shainnel O. Eans,Lisa L. Wilson,Satyanarayana M Chintala,Marta Filizola,Richard M. van Rijn,Elyssa B. Margolis,Bryan L. Roth,Jay P. McLaughlin,Tao Che,Tao Che,Dalibor Sames,Jonathan A. Javitch,Susruta Majumdar +24 more
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The Life Cycle of the Mu-Opioid Receptor
TL;DR: The knowledge of the life cycle of the mu-opioid receptor, including its biogenesis, trafficking to and from the plasma membrane, and how the regulation of these processes impacts its function and is related to pathophysiological conditions is summarized.
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Altered Signaling in the Descending Pain-modulatory System after Short-Term Infusion of the μ-Opioid Agonist Remifentanil.
TL;DR: These findings demonstrate that, already subsequent to a short-term infusion of the μ-opioid receptor agonist remifentanil, signaling in the descending pain-modulatory system is fundamentally altered and that these changes are directly related to the behavioral sensitivity to pain.
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