Before you read this, I apologize in advance for any repetitiveness. I was writing this entry from memory and doing research at the same time
_________I have heard different things about buprenorphine's affininty and agonism/antagonism of different opiate receptors. Ive heard its primary method of action is based on the fact that buprenorphine has very high binding affinity for the mu receptor and is a
partial agonist (with no mention antagonist properties) at the
mu receptors. "Buprenorphine has been shown to act as an epsilon-opioid antagonist.... Buprenorphine is also a
kappa opioid receptor antagonist, and partial/full agonist at the recombinant human ORL1 nociceptin receptor". Buprenorphine as been show to be approx. 20 to 40 times more potent than morphine, but due to the fact that it is only a partial agonist, these strong analgesic effects are not felt as they would be for a full mu agonist. Buprenorphine's analgesic effect is thought to be mainly due to it's
partial agonist activity at mu opioid receptors: meaning of course, as mentioned, even though buprenorphine has proven to have high analgesic effects than morphine, its full analgesia is not felt.
_________From the research that I have done, it appears to me that buprenorphine is a
'fully' "partial agonist only" on the mu receptors, however on other opiate receptors, buprenorphine appears to be a
full competitive antagonist at the epsilon
(see link at bottom for information about the epsilon receptor) and Kappa opioid receptors. And from my understanding it appears that mu opioid receptors can mediate changes in neuronal excitability of pre-synaptic release of GABA. "GABA transmission in the ventral tegmental area (VTA) is critical for fine tuning the activity of dopamine neurons in response to opioids. However, the precise mechanism by which GABA input shapes opioid reward is poorly understood."(
http://www.jneurosci.org/content/30/42/14029.full). And we know the basics of this because most of us know that benzodiazepines are GABAergic and react with opiates in a synergistic manner.
_________
However, for fully agonistic opioids such as morphine and oxycodone, the main analgesic, euphoric, etc effects of these is due to their
fully agonistic affinity to the mu and kappa receptors respectively;
Side note: This is often a topic of debate because oxycodone (which appears to act mainly on the kappa receptors) in particular produces the anagalgesic effects of other drugs that are primarily mu agonists (i.e. morphine, hydromorphone, diacetylmorphine, the fentanyls, etc). It seems that buprenorphine's main
"analgesic and maintenance" effects are based on the fact that buprenorphine has an
extremely high binding agonistic affinity for the mu receptors whereas it is a sole competitive antagonist at the Kappa receptors (which we have determined above to be the main receptors for the analgesic, euphoric, etc effects of
full agonists such as morphine and oxycodone respectively).
_________So buprenorphine's mechanisms of action are its
partial agonist activity at the mu opioid receptor: and its
partial or full agonist activity at the
"opiate like, but rarely mentioned" ORL1/nociceptin receptors, as well as the delta opioid receptors, (Side note: the Delta receptors to my understanding, mainly mediate opiates' antitussive properties rather than the analgesic properties); however, it has been shown that the opiates that have a higher affinity to delta receptors can cause analgesia to a certain degree, but not to the same degree as mu and kappa receptors. Also, buprenorphine is shown to be a
"competitive" antagonist only at the
kappa opioid receptors..
_________To summarize, buprenorphine has
partial agonistic only effects on the
mu receptors and is a
"partial or full" agonist of the
delta receptors as well as the "opiate like" ORL1/nociceptin receptors. As far as it's antagonist properties go, buprenorphine has proven to be a
full antagonist at the epsilon and kappa receptors. (
As a reminder; the
Kappa receptors are the receptors that oxycodone, in particular, has a high agonistic affinity for and has been shown to be the primary mediator for oxycodone's analgesic, euphoric, etc effects).
Side note regarding the existence of 'epsilon receptors': "the existence of the epsilon receptor has been controversial, and this receptor is generally not recognized as a member of the opioid peptide receptor family because it has not been precisely characterized."
(see http://www.ncbi.nlm.nih.gov/pubmed/11730972 for more info on the epsilon receptors).
_________
In short: Buprenorphine is a known to be a partial mu agonist; a "partial or full" agonist of the 'opiate like' ORL1/nociceptin receptors as well as the delta receptors, and a full antagonist of the Kappa and Epsilon receptors All of these factors (and probably more) are why buprenorphine is considered a partial agonist and anatagonist.