From the Guidelines
Partial agonists, such as buprenorphine, bind to the μ-opioid receptor. This is based on the most recent and highest quality study available, which states that buprenorphine is a partial opioid agonist with a high binding affinity for the μ-opioid receptor 1.
Key Points
- Buprenorphine's high affinity for the μ-opioid receptor diminishes the ability of other more potent full agonist opioids to dislodge it from the receptor 1.
- The blocking of other full opioid agonists is a beneficial property in the treatment of opioid use disorder 1.
- Buprenorphine is available as a sublingual tablet, sublingual film, and 6-month implant that are approved for the treatment of opioid use disorders; a transdermal patch is approved for the treatment of chronic pain 1.
- Partial agonists, like buprenorphine, can act as competitive antagonists by occupying receptors without fully activating them, making them useful in addiction medicine, psychiatry, and pain management 2.
Relevance to Clinical Practice
- The clinical significance of partial agonists lies in their ability to produce a ceiling effect, which often results in a better safety profile with reduced risk of overdose compared to full agonists.
- In the context of real-life clinical medicine, partial agonists like buprenorphine are particularly useful in managing chronic pain and opioid use disorder, as they can provide therapeutic benefits while minimizing adverse effects associated with full receptor activation 1, 2.
From the FDA Drug Label
Buprenorphine Sublingual Tablets contain buprenorphine, a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper.
Partial agonists bind to the mu-opioid receptor. [3] [4]
- Key points: + Buprenorphine is a partial agonist at the mu-opioid receptor. + It also acts as an antagonist at the kappa-opioid receptor.
From the Research
Receptor Binding of Partial Agonists
- Partial agonists bind to various receptors, including the μ-opioid receptor, δ-opioid receptor, κ-opioid receptor, and opioid receptor-like 1 receptor 5, 6, 7
- Buprenorphine, a partial agonist, has a high binding affinity for the μ-opioid receptor, but low efficacy, resulting in a partial effect upon binding 5, 6, 7
- Partial agonists can act as antagonists by competing for receptor binding with full agonists, and their level of activity depends on the level of endogenous receptor activity 8
Specific Receptors Bound by Partial Agonists
- μ-opioid receptor: buprenorphine is a partial agonist with high binding affinity, but low efficacy 5, 6, 7
- δ-opioid receptor: buprenorphine is an antagonist with high binding affinity 5
- κ-opioid receptor: buprenorphine is an antagonist with high binding affinity 5
- Opioid receptor-like 1 receptor: buprenorphine is an agonist with low binding affinity 5, 7
Implications of Partial Agonist Binding
- Partial agonists can provide a unique role in mediating analgesic signaling at spinal opioid receptors while having less of an effect on brain receptors, potentially limiting classic opioid-related adverse events 5
- Partial agonists can be used to treat patients with addiction and decrease the symptoms of withdrawal and risks of overdose and intoxication 6, 8