Emerging pharmacologic mechanisms of buprenorphine to explain experience of analgesia versus adverse effects

Jeffrey Bettinger, PharmD; Himayapsill Batista Quevedo, PharmD; Jacqueline Cleary, PharmD, BCACP

doi:10.5055/jom.2021.0639

Authors

Jeffrey Bettinger, PharmD
Himayapsill Batista Quevedo, PharmD
Jacqueline Cleary, PharmD, BCACP https://orcid.org/0000-0001-5846-6741

DOI:

https://doi.org/10.5055/jom.2021.0639

Keywords:

buprenorphine, G-protein-coupled opioid receptors, β-arrestin, respiratory depression, analgesia, euphoria

Abstract

Buprenorphine’s unique pharmacologic mechanisms of action lend itself to a higher level of complexity than its typical characterization as a partial agonist at μ-opioid receptors. It is well-documented that its additional activity at Δ- and κ-opioid receptors, and opioid receptor ligand 1 may be associated with varying degrees of analgesia and usual opioid-related adverse effects. However, novel downstream molecular and cellular mechanisms from μ-opioid receptor activation contain potential new insights into its overall unique effects. These include buprenorphine’s peculiar ability to induce analgesia at escalating doses, while exhibiting a plateaued effect on respiratory depression, euphoria, gastrointestinal (GI) motility, depression, anxiety, and addictive potential. Thus, this review aims to discuss several of these emerging mechanisms to gain a better understanding of these curious actions, as well as support much of this in vitro evidence with various human clinical trial data to further support buprenorphine’s place on the analgesic ladder.

Author Biographies

Jeffrey Bettinger, PharmD

Pain Management Clinical Pharmacist, Saratoga Hospital Medical Group, Saratoga Springs, New York

Himayapsill Batista Quevedo, PharmD

PGY-2 Pain and Palliative Care Pharmacy Practice Resident, Albany Stratton VA Medical Center, Albany, New York

Jacqueline Cleary, PharmD, BCACP

Assistant Professor, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York

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