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Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids
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    Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids
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    • Samuel Obeng
      Samuel Obeng
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      More by Samuel Obeng
    • Shyam H. Kamble
      Shyam H. Kamble
      Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      Translational Drug Development Core, Clinical and Translational Sciences Institute, University of Florida, Gainesville, Florida 32610, United States
    • Morgan E. Reeves
      Morgan E. Reeves
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
    • Luis F. Restrepo
      Luis F. Restrepo
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
    • Avi Patel
      Avi Patel
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      More by Avi Patel
    • Mira Behnke
      Mira Behnke
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      More by Mira Behnke
    • Nelson J.-Y. Chear
      Nelson J.-Y. Chear
      Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
    • Surash Ramanathan
      Surash Ramanathan
      Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
    • Abhisheak Sharma
      Abhisheak Sharma
      Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      Translational Drug Development Core, Clinical and Translational Sciences Institute, University of Florida, Gainesville, Florida 32610, United States
    • Francisco León
      Francisco León
      Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
    • Takato Hiranita
      Takato Hiranita
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
    • Bonnie A. Avery
      Bonnie A. Avery
      Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
    • Lance R. McMahon*
      Lance R. McMahon
      Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      *For L.R.M.: E-mail, [email protected]
    • Christopher R. McCurdy*
      Christopher R. McCurdy
      Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
      Translational Drug Development Core, Clinical and Translational Sciences Institute, University of Florida, Gainesville, Florida 32610, United States
      *For C.M.C.: E-mail, [email protected]
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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2020, 63, 1, 433–439
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    https://doi.org/10.1021/acs.jmedchem.9b01465
    Published December 13, 2019
    Copyright © 2019 American Chemical Society

    Abstract

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    Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.

    Copyright © 2019 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01465.

    • Experimental procedures and spectroscopic data for the kratom alkaloids, details of the PK studies, and assay protocols for the binding and in vivo studies (PDF)

    • Molecular formula strings (CSV)

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    This article is cited by 105 publications.

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    https://doi.org/10.1021/acs.jmedchem.9b01465
    Published December 13, 2019
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