Format

Send to

Choose Destination
J Pain. 2015 Dec;16(12):1321-1333. doi: 10.1016/j.jpain.2015.09.004. Epub 2015 Oct 9.

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

Author information

1
Department of Psychology, McGill University, Montreal, Quebec, Canada; Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada; Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada. Electronic address: lj.martin@utoronto.ca.
2
Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada; Department of Anesthesiology, McGill University, Montreal, Quebec, Canada.
3
Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, North Carolina.
4
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina.
5
Department of Psychology, McGill University, Montreal, Quebec, Canada; Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada; Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
6
Department of Psychology, McGill University, Montreal, Quebec, Canada; Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
7
Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada; Department of Anesthesiology, McGill University, Montreal, Quebec, Canada; Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, North Carolina.

Abstract

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.

KEYWORDS:

Pain; antinociception; bupranolol; propranolol; β-adrenergic receptors

PMID:
26456674
DOI:
10.1016/j.jpain.2015.09.004
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center