Controlled substance (opiate). Analgesic (narcotic)
ChEBI: Oxymorphone is a morphinane alkaloid.
Thebaine is dissolved in aqueous formic acid and treated with 30% H2O2; neutralization with aqueous ammonia gives 14-hydroxycodeinone. It is hydrogenated to give oxycodone. 90 ml of concentrated hydrobromic acid are heated to 90°C. 9 grams of 14-hydroxydihydrocodeinone (oxycodone) are then added under stirring and the mixture is quickly heated to 116°C and kept at this temperature under reflux condenser for 20 minutes, with continued stirring. The resulting brown solution is diluted with about 90 ml of water and chilled with ice. Aqueous 10% sodium hydroxide solution is now added to alkaline reaction and the liquid is extracted 3 times with 100 cc portions of chloroform. The layers are separated and the aqueous phase is filtered and acidified by the addition of concentrated aqueous hydrochloric acid, treated with charcoal and filtered.
The filtrate is treated with concentrated aqueous ammonia until the mixture gives a pink color on phenolphthalein paper. The liquid is extracted seven times with 100 cc portions of chloroform, the extracts are combined, dried with anhydrous sodium sulfate and evaporated. The residue is dissolved in ethanol by refluxing and the ethanol evaporated nearly to dryness. 100 cc of benzene are then added, the mixture is refluxed for ? hour and set aside for crystallization. After cooling, the desired compound is collected by filtration, 2.3 grams of a white crystalline powder are obtained; MP 245° to 247°C. This powder consisting of 14-hydroxydihydromorphinone can be purified by recrystallization from benzene, ethylacetate or ethanol. From benzene it generally forms diamond shaped platelets, while needles are obtained from ethylacetate.
On heating, the crystals are discolored from about 200°C on, and melt at 246° to 247°C to a black liquid, which decomposes with strong volume increase if the temperature is raised further by a few degrees.
Numorphan (Endo); Opana (Endo).
Oxymorphone is 10 times as potent as morphine,
with actions similar to those of hydromorphone.
Oxymorphone, however, has little antitussive activity,
and as such is a useful analgesic in patients with pulmonary
disease who need to retain the ability to cough.
Oxymorphone is the 14 beta-hydroxyl version of hydromorphone,analogous to the hydrocodone, oxycodone pair discussedabove. Although the addition of the 14 beta-hydroxylgroup to hydrocodone (30 mg) yielded oxycodone (20 mg),a more potent drug, the opposite is true for the conversion ofhydromorphone (7.5 mg) to oxymorphone (10 mg). The reasonfor this is that the oral bioavailability of oxymorphone(10%) is lower than that of hydromorphone (35%) becauseof decreased absorption and increased first-pass metabolism.Presumably, the addition of the OH group does increaseits binding affinity at the receptor as the injectableform of oxymorphone (1 mg) is more potent than injectablehydromorphone (1.5 mg).
Oxymorphone is available as a suppository (5 mg), an injection(1 mg/mL), an immediate-release tablet (5 mg, 10mg), and in 2003 the FDA approved a sustained release formulation(Opana ER 5 mg, 10 mg, 20 mg, and 40 mg). The12-hour coverage of the extended release tablet provides anotheroption for those patients suffering from chronic pain.The side effect profile of the extended release formulationsof morphine, oxycodone, and oxymorphone are similar, andthere appears to be no clear advantage of one over the other.
