Buprenorphine-like opioid

Attention was drawn to the 4 -substituted 14-cinnamoylamino-17-cyclopropyl-methyl-7,8-dihydronorcodeinones and equivalent morphinones (40) (Fig. 3). Of particular interest to Reckitt and Colman s target of buprenorphine-like opioid activity were the dihydrocodeinones (40a-c) from which the 4 -chloro derivative, called methoclocinnamox (40a, MC-CAM), was selected for detailed study. The Reckitt and Colman group had shown the three 4 -substituted dihydrocodeinones (40a-c) to be predominantly MOR partial agonists of long duration in vivo [14], Importantly, MC-CAM showed bell-shaped dose-response curves in both tail withdrawal and tail pressure antinociceptive assays. In this respect and in the inability of naltrexone to reverse its antinociceptive effect, as well as its long-lived morphine antagonism, its similarity to buprenorphine was demonstrated. 

Withdrawal from opioids is uncomfortable but unlikely to be fatal unless the patient has underlying medical problems. Administer the COWS to determine the severity of withdrawal. Those with a score of 5 or less require no pharmacologic intervention, while those with scores from 6 to 24 are likely to benefit from either a symptoms-based approach or the initiation of buprenorphine. Those with scores greater than 25 should receive either buprenorphine or an alternative full p agonist. 

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. 

Patients taking methadone or other long-acting opioids Withdrawal appears more likely in patients maintained on higher doses of methadone (more than 30 mg) and when the first buprenorphine dose is administered shortly after the last methadone dose. 

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... 

Sudden deaths in patients who abuse opioids are frequently associated with ingestion of other CNS depressants, particularly benzodiazepines. Cases have been reported with buprenorphine, oxycodone, and tramadoF taken with various benzodiazepines. It has not been established exactly why this occurs, but both pharmacodynamic and pharmacokinetic mechanisms are possible. The deleterious interaction of benzodiazepines and opioids on respiration is possibly due to central effects and/or additive actions on the different neuromuscular components of respiration. For buprenorphine, it is considered most likely that ex-... 

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