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Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.

Publication ,  Journal Article
Martin, LJ; Piltonen, MH; Gauthier, J; Convertino, M; Acland, EL; Dokholyan, NV; Mogil, JS; Diatchenko, L; Maixner, W
Published in: J Pain
December 2015

UNLABELLED: Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective β-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and bupranolol for all 3 β-ARs. Of the agents examined, S-bupranolol is superior in terms of its antinociceptive effect and exhibited fewer side effects than propranolol or its associated enantiomers. In contrast to propranolol, S-bupranolol exhibited negligible β-AR intrinsic agonist activity and displayed a full competitive antagonist profile at β(1)/β(2)/β(3)-ARs, producing a unique blockade of β(3)-ARs. We have shown that S-bupranolol is an effective antinociceptive agent in mice without negative side effects. The distinctive profile of S-bupranolol is most likely mediated by its negligible β-AR intrinsic agonist activity and unique blockade of β(3)-AR. These findings suggest that S-bupranolol instead of propranolol may represent a new and effective treatment for a variety of painful conditions. PERSPECTIVE: The S enantiomer of bupranolol, a β-receptor antagonist, shows greater antinociceptive efficacy and a superior preclinical safety profile and it should be considered as a unique β-adrenergic receptor compound to advance future clinical pain studies.

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Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

December 2015

Volume

16

Issue

12

Start / End Page

1321 / 1333

Location

United States

Related Subject Headings

  • Stereoisomerism
  • Receptors, Adrenergic, beta
  • Propranolol
  • Pain Measurement
  • Nociception
  • Mice
  • Male
  • Female
  • Disease Models, Animal
  • Bupranolol
 

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Martin, L. J., Piltonen, M. H., Gauthier, J., Convertino, M., Acland, E. L., Dokholyan, N. V., … Maixner, W. (2015). Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers. J Pain, 16(12), 1321–1333. https://doi.org/10.1016/j.jpain.2015.09.004
Martin, Loren J., Marjo H. Piltonen, Josee Gauthier, Marino Convertino, Erinn L. Acland, Nikolay V. Dokholyan, Jeffrey S. Mogil, Luda Diatchenko, and William Maixner. “Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.J Pain 16, no. 12 (December 2015): 1321–33. https://doi.org/10.1016/j.jpain.2015.09.004.
Martin LJ, Piltonen MH, Gauthier J, Convertino M, Acland EL, Dokholyan NV, et al. Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers. J Pain. 2015 Dec;16(12):1321–33.
Martin, Loren J., et al. “Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.J Pain, vol. 16, no. 12, Dec. 2015, pp. 1321–33. Pubmed, doi:10.1016/j.jpain.2015.09.004.
Martin LJ, Piltonen MH, Gauthier J, Convertino M, Acland EL, Dokholyan NV, Mogil JS, Diatchenko L, Maixner W. Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers. J Pain. 2015 Dec;16(12):1321–1333.
Journal cover image

Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

December 2015

Volume

16

Issue

12

Start / End Page

1321 / 1333

Location

United States

Related Subject Headings

  • Stereoisomerism
  • Receptors, Adrenergic, beta
  • Propranolol
  • Pain Measurement
  • Nociception
  • Mice
  • Male
  • Female
  • Disease Models, Animal
  • Bupranolol