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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Broad-spectrum analgesic efficacy of IBNtxA is mediated by exon 11-associated splice variants of the mu-opioid receptor gene
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TL;DR: Strong analgesic activity is shown, in a wide range of preclinical pain assays, of the 6‐transmembrane‐acting compound IBNtxA, supportive of the potential value of 6‐TM‐acting drugs as novel analgesics.
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Morphine Regulates Expression of μ-Opioid Receptor MOR-1A, an Intron-Retention Carboxyl Terminal Splice Variant of the μ-Opioid Receptor (OPRM1) Gene via miR-103/miR-107
TL;DR: Chronic morphine treatment significantly upregulated miR-103 and mi-107 levels, leading to downregulation of polyribosome-associated MOR-1A in both Be(2)C cells and the striatum of a morphine-tolerant mouse, providing a new perspective on understanding the roles of miRNAs and OPRM1 splice variants in modulating the complex actions of morphine in animals and humans.
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Assessment of structure-activity relationships and biased agonism at the Mu opioid receptor of novel synthetic opioids using a novel, stable bio-assay platform
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Jeremy J. Roach,Ryan A. Shenvi +1 more
TL;DR: A review of analogs of the salvinorin chemotype and their effects on selectivity, affinity and potency can be found in this article, where the authors also discuss the effects of different combinations of salvinors on the human kappa-opioid receptor.
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