Most of the structural changes to the methadone skeleton resulted in compounds with decreased opioid potencies, thus most of these compounds, with the exception of LAAM were not developed. Propoxyphene is a derivative of methadone marketed in 1957 as the enantiomerically pure (2S, 3R)-
4-(Dimethylamino)-3-methyl-1,2,-diphenyl-2-butanol propionate (ester). It is only about 1/10th as potent as morphine as an analgesic yet retains all the same opioid adverse effects. One propoxyphene 65-mg capsule has the same analgesic effect of 650 mg of aspirin or 1,000 mg of acetaminophen, thus overdoses of propoxyphene can occur if patients do not follow the prescribed dose. Between 1981 and 1999, 2,110 accidental deaths were reported because of propoxyphene. Propoxyphene and all propoxyphene combination products are listed using the Beers criteria as medications to avoid in patients older than 65 years of age.96 The metabolism of propoxyphene also contributes to the potential dangers of the drug. Propoxyphene is metabolized via N-demethylation to form norpropoxyphene. Norpropoxyphene has been shown to build up in cardiac tissues and result in naloxone-insensi-tive cardiotoxicity.97 The weak analgesic action and potential risk to the patient have some health practitioners advocating to remove all drugs containing propoxyphene from the mar-ket.98 The hydrochloride salt is marketed as Darvon, the nap-sylate salt as Darvon-N, both salts are also available combined with acetaminophen (Darvocet, Darvocet-N) and a propoxyphene, aspirin, caffeine product is also available.
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