Analgesics buprenorphine

The quest for compounds that combined the analgesic properties of morphine, were nonaddictive, and lacked the side effects of nalorphine, led to the development of the dmgs shown in Table 3. These compounds have both agonist and antagonist activities. Nalbuphine (14) (23) and buprenorphine... 

Jasinski DR, PevnickJS, Griffith JD Human pharmacology and abuse potential of the analgesic buprenorphine. Arch Gen Psychiatry 35 501-516, 1978 Jasinski DR, Johnson RE, Kocher TR Clonidine in morphine withdrawal differential effects on signs and symptoms. Arch Gen Psychiatry 42 1063-1066, 1983... 

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. 

Buprenorphine does not cause dependence in humans [96]. Unbke morphine, buprenorphine desensitizes the /< receptor coupling to adenylyl cyclase [80]. The desensitization occurs in the absence of any receptor internalization or downregu-lation [80]. The desensitization of the /x receptor may be the underlying basis for why buprenorphine does not cause a heightened adenylyl cyclase activity in // receptor-responsive cells. Buprenorphine s unique cellular regulation of the // receptor may explain its ability to be a non-addictive analgesic as well as its usefulness in treating opiate dependence. 

Buprenorphine is a weak analgesic [91], which precludes its ability to replace morphine in the treatment of chronic pain. However, development of compounds that interact with /u receptors in a similar manner as buprenorphine but that are more effective agonists and analgesics could lead to the development of drugs that can be used for the treatment of chronic pain but which have little or no abuse potential. 

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... 

AccessMedicine Print Chapter 31. Opioid Analgesics Antagonists Parenteral 0.5 mg/mL for injection Buprenorphine (Buprenex, others)... 

A new addition to this category is buprenorphine (Buprenex). This drug partially activates mu receptors but is an antagonist at kappa receptors. Because of these selective effects, buprenorphine has been advocated not only as an analgesic, but also as a treatment for opioid dependence and withdrawal.26 84 The use of this drug in treating opioid addiction is discussed in more detail later in this chapter. 

Patients who have received hydromorphone for long periods of time or those with confirmed opioid dependency should not receive the so-called agonist/antagonist analgesics, such as nalbuphine, pentazocine, butorphanol, dezocine, and buprenorphine. The use of these drugs in these patients can intensify withdrawal symptoms. 

A number of narcotic antagonists based on the morphinan stmcture have been marketed—for example, Buprenorphine, Naloxone, Naltrexone, and Nalorfine. Nalmefene is being pursued for the treatment of alcohol abuse. Oxycodone, and its precursor Codeine, are marketed, with restrictions, as analgesics. noSee Chapter 9, Table 3. 

As nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate ALPE, the administration of NSAIDs should be avoided even after onset. When patients require analgesic agents, synthetic opioid agonist/antagonist analgesics (pentazocine hydrochloride or buprenorphine hydrochloride) should be administered. 

It has long been known that only morphine and codeine possess analgesic properties, whereas thebaine acts as a convulsant, similar to strychnine [16]. However, analogues produced from thebaine have provided some of the more interesting and clinically useful dmgs such as buprenorphine (see Section 11.5). Indeed, an early structure-activity relationship was realized between morphine and its methylated phenolic relative, codeine. Codeine (see below) is known to have about one-tenth the analgesic activity of morphine, and was also less likely to produce addiction. Additionally, an early diacetylated analogue of morphine, heroin (6) (Fig. 11.2), demonstrated an increased potency but also an increased addictive potential. 

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