Buprenorphine is a partial mu-opioid agonist otherwise known as a mixed agonist-antagonist. For the purposes of this thread the substance called buprenorphine will be referred to as "Bupe." Bupe is derived from the alkaloid of the opium poppy called Thebaine which is not an opioid it self. Examples of Thebaine derivatives include
-Full antagonists Naloxone and Naltrexone
-Semi/synthetic full agonists Oxycodone,Oxymorphone, Hydrocodone, Hyrdromorphone
-Partial agonists Nalbuphine and Buprenorphine
Buprenorphine has a unique pharmacological profile with activation of the mu-opioid receptor compared to full agonist activation induced by morphine. once converted to norbuprenorphine. Though bupe has a higher affinity for the mu-opioid receptor compared to morphine. Buprenorphine is a partial agonist but a pretty potent analgesic itself without even being converted to norbupe.
Buprenorphine has also now been shown to act as an epsilon-opioid antagonist. Buprenorphine is also a κappa-opioid receptor antagonist, and partial/full agonist at the recombinant human ORL1 nociceptin receptor.
Metabolization of buprenorphine occurs in the liver and metabolized into the full mu opioid agonist nor-buprenorphine by the liver enzyme/s CYP3A4 (CYP2C8 enzyme involved)
Norbuprenorphine is a full mu opioid receptor agonist but also an agonist at the delta opioid receptor. This is what the stimulatory perceived effects may be largely attributed to and explained by bupes' thebaine based structure.
Warning: Precipitated Withdrawal.
Because buprenorphine has partial agonist activity it causes Precipitated withdrawal syndrome where buprenorphine itself(Not naloxone) causes displacement of full agonists like morphine due to the higher affinity for the opioid receptors compared to most conventional opioid agonists.
-sublingual: 40-50%(Ethanol Solution)
-sublingual: 35-40% (Tablets)
Suboxone is a orange flavored sublingual formula consisting of Buprenorphine and Naloxone.
Dosages formulated in: 2mgBupe/.05mgs Naloxone and 8mg Bupe/2mg naloxone.
: The naloxone contained in suboxone is mostly inactive when suboxone is used as intended(sublingual). Some people do experience naloxone sensitivity and irritation. Since the bupe is absorbed in the mocous membranes it is likely that when bupe is used intranasally the naloxone is probably not active in that situation either or mostly inert.
Subutex is a chalky white flavored tablet formulated to just contain buprenorphine but has the same precipitated withdrawal associations as suboxone. Because bupe is a partial agonist it also has antagonist activity. Buprenorphine is responsible for the the precipitated withdrawal syndrome not bupes active metabolite norbuprenorphine which is a full agonist.
Note: Precipitated withdrawal is only likely to occur in those individuals who are dependent on full agonist substances like morphine, oxycodone, methadone, diacetylmorphine, hydrocodone, hydromorphone, oxymorphone etc. The dependent individual should wait until the full agonist is completely out of their system and they are in full withdrawal before switching to a buprenorphine containing formulation. For short acting full agonists like morphine, oxycodone, etc it is recommended to wait atleast 24 hours.
Longer acting full agonists especially methadone are more tricky. Considering methadone potency it is recommended that the opioid dependent individual should wean down to at least or less than 30mgs of methadone. Also it is of great importance if the person has been on a chronic daily dose(1 month or more) of methadone that they should wait at least 72 hours before switching but 5-8 days is a more reasonable wait for those who metabolize and eliminate methadone slower or have been on it for a very long time.
The naloxone contained within suboxone is commonly attributed by buprenorphine user and even the doctor as the sole cause of precipitated withdrawal; however. it is more likely that buprenorphine itself is culprit for precipitated withdrawal especially when no injection type use is occurring.
Naloxone is known to antagonize buprenorphine and even given in the event of a buprenorphine overdose; however; naloxone has a very short half life lasting about 60 minutes.
Some have said buprenorphine may have a higher affinity for the mu opioid receptor compared to naloxone anyways but more recent studies show that it is likely the half life of naloxone that results in the bupe eventually winning out in the system.
To be continued