Ketobemidone: Difference between revisions

Line 9:

==History and culture==

Ketobemidone was first synthesized during World War II by German scientists at the I.G. Farbenindustrie laboratory in Höchst, 1942.<ref>[https://worldwide.espacenet.com/patent/search/family/004472963/publication/GB609763A?q=pn%3DGB609763 GB patent 609763], "Manufacture of piperidyl ketones", published 1948-10-06, assigned to Ciba Ltd.</ref>

Ketobemidone was first synthesized during World War II by German scientists at the I.G. Farbenindustrie laboratory in Höchst, 1942.<ref>[https://worldwide.espacenet.com/patent/search/family/004472963/publication/GB609763A?q=pn%3DGB609763 GB patent 609763], "Manufacture of piperidyl ketones", published 1948-10-06, assigned to Ciba Ltd.</ref> The first study of it in humans was published in 1946,<ref>US patent 2486796, Meischer, K.; Kaegi, H., "Esters of 1-alkyl-4-hydroxyphenyl-piperidil-4-ketones", issued 1949-11-01</ref> and it was introduced in clinical medicine shortly after.

Today, Pfizer produces ketobemidone under the brand names Ketogan and Ketorax in tablet and suppository form as well as injection liquids.{{citation needed}}

Line 16:

Ketobemidone's substitutive name is is 1-methyl-4-(3-hydroxyphenyl)-4-propionylpiperidine. The substance is primarily available as a white, powdered hydrochloride salt.<ref>William Andrew Publishing (2013). [https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA936 "Cetobemidone"] (excerpt). ''Pharmaceutical Manufacturing Encyclopedia.'' Elsevier. ISBN [https://en.wikipedia.org/wiki/Special:BookSources/9780815518563 9780815518563].</ref>

The synthesis occurs by alkylating (3-methoxyphenyl)acetonitrile with bis(2-chloroethyl)methylamine, followed by a reaction with ethylmagnesium bromide, and finally O-demethylation with hydrobromic acid.

==Pharmacology==

Ketobemidone is metabolized in the liver by N-demethylation, ringhydroxylation, O-methylation, and O-conjugation. The principal phase 1 reaction is N-demethylation, and it is also metabolized by conjugation of the phenolic hydroxyl group.<ref>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.'' '''9''' (4): 376–80. PMID [https://pubmed.ncbi.nlm.nih.gov/6114838 6114838].</ref> Primary metabolites of ketobemidone are norketobemidone, 4'-hydroxyketobemidone, and hydroxymethoxyketobemidone. The metabolites' pharmacological activity is unknown.<ref name=":0">https://bok.fass.se/LIF/product?userType=0&nplId=19930507000075</ref>

The elimination half-life of ketobemidone is 2 to 2.5 hours for both intravenous and oral administration.<ref name=":0" />

The elimination half-life of ketobemidone is 2 to 2.5 hours for both intravenous and oral administration.<ref name=":0" /> 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.

==Subjective effects==

{{effectStub}}{{Preamble/SubjectiveEffects}}<nowiki> {{effects/base</nowiki>

@@ Line 9: / Line 9: @@
 ==History and culture==
-Ketobemidone was first synthesized during World War II by German scientists at the I.G. Farbenindustrie laboratory in Höchst, 1942.<ref>[https://worldwide.espacenet.com/patent/search/family/004472963/publication/GB609763A?q=pn%3DGB609763 GB patent 609763], "Manufacture of piperidyl ketones", published 1948-10-06, assigned to Ciba Ltd.</ref>
+Ketobemidone was first synthesized during World War II by German scientists at the I.G. Farbenindustrie laboratory in Höchst, 1942.<ref>[https://worldwide.espacenet.com/patent/search/family/004472963/publication/GB609763A?q=pn%3DGB609763 GB patent 609763], "Manufacture of piperidyl ketones", published 1948-10-06, assigned to Ciba Ltd.</ref>  The first study of it in humans was published in 1946,<ref>US patent 2486796, Meischer, K.; Kaegi, H., "Esters of 1-alkyl-4-hydroxyphenyl-piperidil-4-ketones", issued 1949-11-01</ref> and it was introduced in clinical medicine shortly after.
 Today, Pfizer produces ketobemidone under the brand names Ketogan and Ketorax in tablet and suppository form as well as injection liquids.{{citation needed}}
@@ Line 16: / Line 16: @@
 Ketobemidone's substitutive name is is 1-methyl-4-(3-hydroxyphenyl)-4-propionylpiperidine. The substance is primarily available as a white, powdered hydrochloride salt.<ref>William Andrew Publishing (2013). [https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA936 "Cetobemidone"] (excerpt). ''Pharmaceutical Manufacturing Encyclopedia.'' Elsevier. ISBN [https://en.wikipedia.org/wiki/Special:BookSources/9780815518563 9780815518563].</ref>
+The synthesis occurs by alkylating (3-methoxyphenyl)acetonitrile with bis(2-chloroethyl)methylamine, followed by a reaction with ethylmagnesium bromide, and finally O-demethylation with hydrobromic acid.
 ==Pharmacology==
 Ketobemidone is metabolized in the liver by N-demethylation, ringhydroxylation, O-methylation, and O-conjugation. The principal phase 1 reaction is N-demethylation, and it is also metabolized by conjugation of the phenolic hydroxyl group.<ref>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.'' '''9''' (4): 376–80. PMID [https://pubmed.ncbi.nlm.nih.gov/6114838 6114838].</ref> Primary metabolites of ketobemidone are norketobemidone, 4'-hydroxyketobemidone, and hydroxymethoxyketobemidone. The metabolites' pharmacological activity is unknown.<ref name=":0">https://bok.fass.se/LIF/product?userType=0&nplId=19930507000075</ref>
-The elimination half-life of ketobemidone is 2 to 2.5 hours for both intravenous and oral administration.<ref name=":0" />
+The elimination half-life of ketobemidone is 2 to 2.5 hours for both intravenous and oral administration.<ref name=":0" /> 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.
 ==Subjective effects==
 {{effectStub}}{{Preamble/SubjectiveEffects}}<nowiki> {{effects/base</nowiki>