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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Martin, LJ; Piltonen, MH; Gauthier, J; Convertino, M; Acland, EL; Dokholyan, NV; Mogil, JS; Diatchenko, L; Maixner, W

Published Date

  • December 2015

Published In

Volume / Issue

  • 16 / 12

Start / End Page

  • 1321 - 1333

PubMed ID

  • 26456674

Pubmed Central ID

  • 26456674

Electronic International Standard Serial Number (EISSN)

  • 1528-8447

Digital Object Identifier (DOI)

  • 10.1016/j.jpain.2015.09.004


  • eng

Conference Location

  • United States