Separation of Binding Affinity and Intrinsic Activity of the Potent μ-Opioid 14-Methoxymetopon

  title={Separation of Binding Affinity and Intrinsic Activity of the Potent $\mu$-Opioid 14-Methoxymetopon},
  author={Loriann Mahurter and Carrie Garceau and Jacqueline Marino and Helmut Schmidhammer and Géza Tóth and Gavril W. Pasternak},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={247 - 253}
Receptor binding studies of 5,14-O-dimethyloxymorphone (14-methoxymetopon) in brain membranes have established its high affinity for μ-binding sites, but its analgesic potency far exceeds the modest increase in binding affinity relative to other opioids. The current study has established the selectivity of [3H]14-methoxymetopon for μ sites in calf striatal membranes and for a number of full-length splice variants of the cloned murine μ-opioid receptor 1 (mMOR-1) in transfected cell lines. The… 

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Signal transduction efficacy of the highly potent mu opioid agonist 14-methoxymetopon.
Highly potent novel opioid receptor agonist in the 14-alkoxymetopon series.
Classification of multiple morphine and enkephalin binding sites in the central nervous system.
  • B. Wolozin, G. Pasternak
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1981
Findings suggest a common site that binds both opiates and enkephalins equally well and with highest affinity (Kd values, less than 1 nM), which appears to be the site responsible for analgesia under normal circumstances.
14-Methoxymetopon, a very potent mu-opioid receptor-selective analgesic with an unusual pharmacological profile.
Purification and partial amino acid sequence of a mu opioid receptor from rat brain.
Opiate receptor binding: Enzymatic treatments that discriminate between agonist and antagonist interactions
Observations suggest that a major action of enzymatic treatments is to enhance the sensitivity of opiate agonist binding to sodium.
Binding characteristics of [3H]14‐methoxymetopon, a high affinity µ‐opioid receptor agonist
The highly potent µ‐opioid receptor agonist 14‐methoxymetopon was prepared in tritium labelled form by a catalytic dehalogenation method resulting in a specific radioactivity of 15.9 Ci/mmol and would be an important and useful tool in probing µ‐operative receptor mechanisms, as well as to promote a further understanding of the opioid system at the cellular and molecular level.
Molecular cloning and functional expression of a mu opioid receptor from rat brain