Buprenorphine receptor, binding

Opioid receptor binding Buprenorphine has a mixed agonistic-antagonistic action profile with a high affinity for the p-, k-, and 5-opioid receptors (Huang et al., 2001). An approximately 100-fold lower affinity was observed for the ORL1-receptor. The compound dissociates slowly from the receptor which may explain some peculiarities in its pharmacological actions. 

It appears from the spectral map that the K-receptor is a highly specific receptor which produces strong contrasts in binding affinities of opioid analgesics. The contrast is most evident in ketazocine, ethylketazocine and buprenorphine which possess much more affinity for the K-receptor than for the two others. The contrast is also strong with dihydromorphine, beta-endorphin, an enkephalin analog and two experimental compounds (LY and FK) which have little or no affinity for the K-receptor. 

In October 2002, the FDA approved two new medications for treating opiate addiction, both developed by Reckitt Benckiser Pharmaceuticals. The new drugs, Subutex (buprenorphine hydrochloride) and Suboxone tablets (buprenorphine hydrochloride and naloxone hydrochloride) contain buprenorphine, a partial opioid agonist. Like methadone, buprenorphine binds to the brain s opioid receptors, but produces significantly reduced pleasurable effects than heroin. 

Pharmacology Buprenorphine is a semisynthetic centrally acting opioid analgesic derived from thebaine a 0.3 mg dose is approximately equivalent to 10 mg morphine in analgesic effects. Buprenorphine exerts its analgesic effect via high affinity binding of CNS opiate receptors. 

Buprenorphine is a semi-synthetic derivative of thebaine, one of the opium alkaloids. It is approximately 30 times as potent as morphine. A dose of 0.3 mg intramuscularly has a duration of analgesic action of 6-18 h. Buprenorphine is also effective sublingually. The average bio-availability by this route is about 55%, but absorption is slow and the time to achieve peak plasma concentrations is variable, with a range of 90-360 min. The onset of action is rather slow (5-15 min) after both intramuscular and intravenous administration, possibly due to slow receptor association. Buprenorphine binds to and dissociates from the p receptor very slowly, which may account for its low potential for physical abuse. It also means that buprenorphine-induced respiratory depression is difficult to reverse with naloxone, even with very high doses. Doxapram may in these circumstances be useful. Drowsiness and dizziness are the most common side effects, although they rarely... 

Although buprenorphine [byou preh NOR feen] is classified as a partial agonist acting at the p receptor, it behaves like morphine in naive patients. However, it can also antagonize morphine. Buprenorphine is administered parenterally and has a long duration of action because of its tight binding to the receptor. It is metabolized by the liver and excreted in the bile and urine. Adverse effects include respiratory depression, decrease (or, rarely, increase) in blood pressure, nausea and dizziness. 

Buprenorphine is a semi-synthetic, partial mu-agonist, highly lipophilic, opioid drug. Because it is a partial agonist, when buprenorphine competes with morphine or heroin for mu-receptors it can reduce their maximum effect. Buprenorphine binds strongly to mu and kappa opiate receptors it associates with the mu-receptor slowly (30 minutes), but with high affinity, low intrinsic activity and slow and incomplete dissociation. The slow dissociation from the receptor probably limits the intensity of withdrawal by preventing the rapid... 

Naloxone is a pure competitive antagonist at all opioid receptors, notably the p- and K- receptors it has no agonist activity. Naloxone antagonises both agonist and partial agonist opioids (although it may not be sufficient to reverse the effects of buprenorphine in overdose, so tenaciously does the latter drug bind to receptors). It induces an acute withdrawal syndrome in opioid-dependent subjects. 

Buprenorphine is a partial agonist at p receptors, with high binding affinity that provides a long duration of action. Buprenorphine (0.003-0.006 mg/kg i.v.) like other opioids can be combined with another sedative, such as xylazine (p. 268) or acepromazine (p. 271), but because of the long duration of effect of buprenorphine compared with other opioids, acepromazine... 

Buprenorphine binds slowly to analgesic receptors, but once it does bind, it binds very strongly. As a result, less buprenorphine is required to interact with a certain percentage of analgesic receptors than morphine. 

Pentazocine interacts with the p, and k receptors in the same way, but is able to switch on the k receptor more strongly. It too suffers the drawback that it switches on the a receptor. Buprenorphine is slightly different. It binds strongly to all three analgesic receptors and acts as an antagonist at the A (see below) and k receptors, but... 

Buprenorphine p agonist— partial ++(+) + + Long action (binds tightly to receptor), possible use in maintenance... 

Buprinorphine is a semisynthetic opioid analgesic derived from thebaine. It binds readily to the opioid receptors in the CNS but dissociates from them slowly, which may be responsible for its long duration of action. Buprenorphine (0.3 mg DVt) exerts its analgesic actions in 15 minutes and has a duration of action of 6 hours. It is bound to plasma proteins to the extent of 96%, is metabolized in the liver to a certain extent (N-dealkylmetabolite), and is excreted unchanged in the feces. Buprenorphine causes respiratory depression and elevates cerebrospinal pressure (contraindicated in head injury or conditions where intracranial pressure may be high). 

Buprenorphine is an opioid agonist-antagonist analgesic. Its analgesic effect is caused by binding to opiate receptors in the CNS. Antagonist effects decrease its abuse potential. It is indicated in tablet treatment of opioid dependence injection relief of moderate to severe pain. 

Naloxone is not an effective antagonist to buprenorphine because of the latter s high binding affinity to opioid receptors. 

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