Morphine partial agonists

Morphine antagonists and partial agonists. The effects of opioids can be abolished by the antagonists naloxone or naltrexone (A), irrespective of the receptor type involved. Given by itself, neither has any effect in normal subjects however, in opioid-dependent subjects, both precipitate acute withdrawal signs. Because of its rapid presystemic elimination, naloxone is only suitable for parenteral use. Naltrexone is metabolically more stable and is given orally. Naloxone is effective as antidote in the treatment of opioid-induced respiratory paralysis. Since it is more rapidly eliminated than most opioids, repeated doses may be needed. Naltrexone may be used as an adjunct in withdrawal therapy. 

The mixed agonist-antagonists and partial agonists differ from morphine in that they (1) produce excita-... 

The actions described below for morphine, the prototypic opioid agonist, can also be observed with other opioid agonists, partial agonists, and those with mixed receptor effects. Characteristics of specific members of these groups are discussed below. 

Codeine,oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. 

Buprenorphine Partial agonist at P-opioid receptors Attenuates acute effects of morphine Oral substitution therapy for opioid-addicts Long half-life (40 h) formulated together with naloxone to avoid illicit IV injections... 

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... 

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