Naltrexone 6-methylene

Pharmacology Nalmefene, an opioid antagonist, is a 6-methylene analog of naltrexone. Nalmefene prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Nalmefene has no opioid agonist activity it does not produce respiratory depression, psychotomimetic effects or pupillary constriction, and no pharmacological activity was observed when it was administered in the absence of opioid agonists. Nalmefene can produce acute withdrawal symptoms in individuals who are opioid-dependent. 

A solution of 3-methylnaltrexone (0.48 g, 1.35 mmol) in methylene chloride (30 ml) was cooled with an ice-water bath, and then added a solution of boron tribromide (5.4 ml, 1 M solution in methylene chloride, 5.4 mmol). The reaction mixture was stirred at rt. for 15 hr, basified with NH4OH, and extracted with methylene chloride (60 ml). The extract was washed with water (2 times 15 ml), dried over anhydrous sodium sulfate, and evaporated in vacuo to dryness to give naltrexone (0.45 g, 98% yield). 

Another universal antagonist is the naltrexone-derived nalmefene (14). This 6-methylene derivative of naltrexone shows higher k opioid receptor affinity [51, 52], Nalmefene is a potent, orally active opioid antagonist with a... 

B. Nalmefene, an injectable methylene analog of naltrexone, was approved In 1995. It is 4 times more potent than naloxone at mu receptors and slightly more potent at kappa receptors. It has a longer elimination half-life (ranging from approximately 8 to 11 hours after IV dosing), and has a duration of action of 1 hours (see Table 111-8). The prolonged effects of nalmefene are related to the slow dissociation from the opioid receptor, which Is not reflected in the AUC plasma curve. 

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