Ketobemidone
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| Systematic (IUPAC) name | |
| 1-[4-(3-hydroxyphenyl)-1-methyl-4-piperidyl]propan-1-one | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | ? |
| Legal status | Schedule I (US) |
| Routes | Oral, rectal, intravenous |
| Pharmacokinetic data | |
| Bioavailability | 34% (oral), 44% (rectal) |
| Identifiers | |
| CAS number | 469-79-4  |
| ATC code | N02AB01 |
| PubChem | CID 10101 |
| ChemSpider | 9697  |
| UNII | PQS1L514CF |
| KEGG | D08100 |
| ChEMBL | CHEMBL47072 |
| Synonyms | Ketobemidone, Cliradon, Cymidon, Ketogan, Ketorax |
| Chemical data | |
| Formula | C15H21NO2 |
| Mol. mass | 247.333 g/mol |
| SMILES | eMolecules & PubChem |
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Ketobemidone (Cliradon, Ketogan, Ketodur, Cymidon, Ketorax, &c.) is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted by its 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, kidney stones and fractures.
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[edit] History
Ketobemidone was first synthesized in 1942 by Eisleb and colleagues[1], at the laboratory of I.G. Farbenindustrie at Hoechst during the Second World War. The first study of it in man was published in 1946,[2] and it was introduced in clinical medicine shortly after.
[edit] Chemistry
Ketobemidone is 1-methyl-4-(3-hydroxyphenyl)-4-propionylpiperidine. It is usually available as the hydrochloride, 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.[3]
[edit] 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[4]. 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 is the same as that for analgesia, for ketobemidone the analgesic dose was well below the euphoric dose.[5] Ketobemidone is mostly used in the Scandinavian countries, with Denmark topping the statistics.[6]
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.[7]
Pfizer manufactures ketobemidone under the tradenames Ketogan and Ketorax. It is available as tablets, suppositories and injection fluid. A sustained release formulation exists sold as Ketodur in some countries containing 10 or 25 mg ketobemidone.
[edit] References
- ^ GB 609763, "Manufacture of piperidyl ketones", published 1948-10-06, assigned to Ciba Ltd.
- ^ US patent 2486796, Karl Meischer, Hans Kaegi, "Esters of 1-alkyl-4-hydroxyphenyl-piperidil-4-ketones", issued 1949-11-01
- ^ Avison, A. W. D.; Morrison, A. L. (1950). "303. Synthetic analgesics. Part VI. The synthesis of ketobemidone". Journal of the Chemical Society (Resumed): 1469. doi:10.1039/JR9500001469.
- ^ "Development of Synthetic Narcotic Drugs". Bulletin on narcotic drugs (UNODC) (1): 11–14. 1956. http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1956-01-01_1_page003.html. Retrieved 2006-09-07.
- ^ Bondesson, Ulf (1982). "Biological fate of ketobemidone in man". Abstracts of Uppsala dissertations from the Faculty of Pharmacy 68.
- ^ "Statistical information on narcotic drugs" (pdf). INCB. 2004. http://www.incb.org/pdf/e/tr/nar/2004/narcotics_part4.pdf. Retrieved 2006-09-07.
- ^ Bondesson, U.; Hartvig, P.; Danielsson, B. (1981). "Quantitative determination of the urinary excretion of ketobemidone and four of its metabolites after intravenous and oral administration in man". Drug metabolism and disposition: the biological fate of chemicals 9 (4): 376–380. PMID 6114838.
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