RESEARCH MONOGRAPH · KDC-MN-350
Buprenorphine
Buprenorphine is a semi-synthetic opioid with an unusual receptor profile that has made it the cornerstone of medication-assisted treatment for opioid use disorder. As a high-affinity partial mu-opioid agonist it activates the receptor enough to suppress withdrawal and craving but with a built-in ceiling on respiratory depression that makes overdose much less likely than with full agonists. Its kappa antagonism may contribute to mood benefit. The combination with naloxone (Suboxone) discourages injection abuse because naloxone is not orally active but blocks opioid effects if injected. Approved for OUD in the US in 2002, it has saved many lives. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Mu-opioid partial agonist + kappa-opioid antagonist
A semi-synthetic mu-opioid partial agonist with kappa-opioid antagonism; the primary medication-assisted treatment for opioid use disorder.
Abstract
Buprenorphine ((2S,6R,7R,14S)-17-cyclopropylmethyl-7-[(S)-1-hydroxy-1,2,2-trimethylpropyl]-6-methoxy-4,5-epoxy-6,14-ethano-morphinan-3-ol; CAS 52485-79-7; molecular formula C29H41NO4; molecular weight 467.65) is a semi-synthetic thebaine-derived mu-opioid partial agonist with concurrent kappa-opioid antagonist and ORL1 (nociceptin receptor) partial agonist activity. Originally approved by the FDA in 1981 as an analgesic; reformulated and approved in 2002 (Subutex, Suboxone) for opioid use disorder. Mu-opioid affinity is high (Ki approximately 0.2 nM) with intrinsic activity approximately 30 percent (partial agonism); the partial agonism produces a ceiling effect on respiratory depression and euphoria, distinguishing buprenorphine safety profile from full agonists like fentanyl or morphine. Long plasma half-life (24 to 60 hours) supports or less-frequent dosing. Suboxone formulation includes naloxone (a mu antagonist with poor sublingual bioavailability) to deter intravenous misuse. Approved for opioid use disorder and chronic pain (transdermal Butrans). The kappa-opioid antagonism is being investigated for treatment-resistant depression. Used as the canonical mu-opioid partial agonist in addiction medicine.
Mechanism of action
High-affinity mu-opioid partial agonist (~30 percent intrinsic activity; ceiling effect on respiratory depression); kappa-opioid antagonist; ORL1 partial agonist. Long plasma half-life.
Reported research dose ranges
Clinical OUD 4 to 24 mg sublingual; analgesia 0.3 to 0.6 mg IV every 6 to 8 hours or 5 to 20 mcg/hour transdermal.
References
- Walsh SL, et al. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 1994.
- Ling W, et al. Buprenorphine maintenance treatment for opioid use disorder. Lancet 2003.
- Fava M, et al. Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder. Mol Psychiatry 2020.
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The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.