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
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References
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Evidence for Separate Involvement of Different μ-Opioid Receptor Subtypes in Itch and Analgesia Induced by Supraspinal Action of Opioids
Tsugunobu Andoh,Yuichi Yageta,Mitsuhiro Konno,Tomomi Yamaguchi-Miyamoto,Hiroki Takahata,Hiroshi Nojima,Hideo Nemoto,Yasushi Kuraishi +7 more
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Richard J. Bodnar,Richard J. Bodnar,Richard J. Bodnar,Dennis Paul,Dennis Paul,Dennis Paul,Gavril W. Pasternak,Gavril W. Pasternak,Gavril W. Pasternak +8 more
TL;DR: Ethylketocyclazocine is a partial mu 1 agonist which lacks the efficacy to elicit analgesia when microinjected into either of the two brain regions alone, but when exposed to several regions at once, EKC is a potent mu 1 analgesic.
Journal ArticleDOI
14-Methoxymetopon, a very potent μ-opioid receptor-selective analgesic with an unusual pharmacological profile
Michael A. King,Wendy Su,Claire L Nielan,Albert Chang,Johannes Schütz,Helmut Schmidhammer,Gavril W. Pasternak,Gavril W. Pasternak +7 more
TL;DR: It is demonstrated that 14-methoxymetopon is a highly potent mu-opioid with a pharmacological profile distinct from that of the traditional mu-OPioid morphine.
Journal ArticleDOI
Selective opioid δ agonists elicit antinociceptive supraspinal/spinal synergy in the rat
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Journal ArticleDOI
Metkephamid (Tyr-D-Ala-Gly-Phe-N(Me)Met-NH2), a potent opioid peptide: Receptor binding and analgesic properties
TL;DR: Blockade of the high affinity (mu1) binding in vivo with high doses of naloxazone dramatically reduces metkephamid's analgesic potency.
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