Ketobemidone is a powerful opioid

Opioid

An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

 analgesic

Analgesic

An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

. Its effectiveness against pain is in the same range as morphine

Morphine

Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

, and it also has some NMDA

NMDA

N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...

-antagonist properties imparted by it's metabolite norketobemidone. This makes it useful for some types of pain that don't respond well to other opioids. The most commonly cited equalisation ratio for analgesic doses is 25 mg of ketobemidone hydrobromide to 60 mg of morphine hydrochloride or sulfate and circa 8 mg of ketobemidone by injection.

It is used for all types of severe pain, such as postoperative, cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, kidney stone

Kidney stone

A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...

s and fracture

Bone fracture

A bone fracture is a medical condition in which there is a break in the continuity of the bone...

s.

History

Ketobemidone was first synthesized in 1942 by Eisleb and colleagues, at the laboratory of I.G. Farbenindustrie

IG Farben

I.G. Farbenindustrie AG was a German chemical industry conglomerate. Its name is taken from Interessen-Gemeinschaft Farbenindustrie AG . The company was formed in 1925 from a number of major companies that had been working together closely since World War I...

 at Hoechst during the Second World War. The first study of it in man was published in 1946, and it was introduced in clinical medicine shortly after.

Chemistry

Ketobemidone is 1-methyl-4-(3-hydroxyphenyl)-4-propionylpiperidine. It is usually available as the hydrochloride

Hydrochloride

In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....

, which is a white powder. It is synthesized by alkylating (3-methoxyphenyl)acetonitrile with bis(2-chloroethyl)methylamine, followed by reaction with ethylmagnesiumbromide, and finally O-demethylation with hydrobromic acid

Hydrobromic acid

Hydrobromic acid is a strong acid formed by dissolving the diatomic molecule hydrogen bromide in water. "Constant boiling" hydrobromic acid is an aqueous solution that distills at 124.3 °C and contains 47.6% HBr by weight, which is 8.89 mol/L. Hydrobromic acid has a pKa of −9, making it a...

.

Pharmacology

Experiments on former addicts indicated it was more addictive than other opioids, so in 1954 the Economic and Social Council took a resolution urging governments to stop manufacture and use of ketobemidone. This result was not in agreement with clinical observations, and another study in 1958 did not find it more addictive than morphine. That study noticed that while for morphine the dose for euphoria

Euphoria (emotion)

Euphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of well-being, elation, happiness, ecstasy, excitement and joy...

 is the same as that for analgesia, for ketobemidone the analgesic dose was well below the euphoric dose.
Ketobemidone is mostly used in the Scandinavia

Scandinavia

Scandinavia is a cultural, historical and ethno-linguistic region in northern Europe that includes the three kingdoms of Denmark, Norway and Sweden, characterized by their common ethno-cultural heritage and language. Modern Norway and Sweden proper are situated on the Scandinavian Peninsula,...

n countries, with Denmark

Denmark

Denmark is a Scandinavian country in Northern Europe. The countries of Denmark and Greenland, as well as the Faroe Islands, constitute the Kingdom of Denmark . It is the southernmost of the Nordic countries, southwest of Sweden and south of Norway, and bordered to the south by Germany. Denmark...

 topping the statistics.

Analgesia after 5-10 mg orally or 5-7.5 mg intravenously lasts 3–5 hours. Ketobemidone is also available in preparations with a spasmolytic, which can improve the analgesia.

Ketobemidone is mainly metabolised by conjugation of the phenolic hydroxyl group, and by N-desmethylation. Only about 13-24% is excreted unchanged after iv. administration.

Pfizer

Pfizer

Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...

 manufactures ketobemidone under the tradenames Ketogan and Ketorax. It is available as tablet

Tablet

A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...

s, suppositories and injection fluid. A sustained release formulation exists sold as Ketodur in some countries containing 10 or 25 mg ketobemidone.