nalbuphine

Absorption

The mean absolute bioavailability was 81% and 83% for the 10 and 20 mg intramuscular doses, respectively, and 79% and 76% following 10 and 20 mg of subcutaneous nalbuphine. Clinical studies show that the duration of analgesic activity of the drug can range from 3 to 6 hours.

Toxicity

Oral, acute LD50 is 1100 mg/kg in dog. Symptoms of overdose include primarily sleepiness and mild dysphoria.

Chemical properties

Pale Yellow Solid

Originator

Nubain,Du Pont,US,1979

The Uses of nalbuphine

Nalbuphine is a mixed opioid agonist-antagonist. Nalbuphine is an analgesic (narcotic).

The Uses of nalbuphine

Mixed opioid agonist-antagonist. Analgesic (narcotic).

Background

A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors. Nalbuphine is the only opioid analgesic that is not a controlled substance in the United States.

Indications

For the relief of moderate to severe pain.

Definition

ChEBI: Nalbuphine is an organic heteropentacyclic compound. It has a role as a mu-opioid receptor antagonist and an opioid analgesic. It derives from a hydride of a morphinan.

Manufacturing Process

To a slurry of 110.5 g of 14-hydroxydihydronormorphinone in 2.5 liters of methylene chloride and 280 ml of triethylamine was added a solution of 106 g of cyclobutanecarboxylic acid chloride in 500 ml of methylene chloride. The temperature of the reaction mixture was maintained at 20°C to 25°C during the addition. After 5 minutes the reaction mixture was brought to reflux and heated for 5 hours.
It was then cooled, washed with water, dried over sodium sulfate and evaporated to dryness. The residue was crystallized from benzene and pentane to give 138.5 g of the dicyclobutanecarbonyl derivative, melting point about 112°C (dec.).
The dicyclobutanecarbonyl derivative (136.7 g) was dissolved in 200 ml of tetrahydrofuran and added dropwise to a suspension of 34.2 g of lithium aluminum hydride in 1 liters of tetrahydrofuran. The temperature of the mixture rose to reflux during the addition. Reflux was maintained for 2 hours after the addition was completed. After cooling, 110 ml of ethyl acetate was added dropwise, followed by 30 ml of water, followed by a solution of 53 g of ammonium chloride in 125 ml of water. The resulting mixture was filtered and the inorganic precipitate was washed with methanol. Evaporation of the combined filtrates gave 66 g of N-cyclobutylmethyl-14-hydroxydihydronormorphinone, melting point 229°C to 231°C.

brand name

Nubain (Endo).

Therapeutic Function

Analgesic

Pharmacokinetics

Nalbuphine is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. Nalbuphine's analgesic potency is essentially equivalent to that of morphine on a milligram basis. The opoioid antagonist activity of nalbuphine is about one-fourth to that of nalorphine and 10 times to that of pentazocine. Nalbuphine by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. Nalbuphine may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.

Metabolism

Not Available