Ketobemidone: Difference between revisions

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{{headerpanel|{{DepressantOD|opiates}}}}

{{headerpanel|{{DepressantOD|opiates}}{{approval}}}}

~~{{stub~~}}

'''Ketobemidone''' (also known by the brand names '''Ketogan''', and '''Ketorax''') is ~~a synthetic~~ [[~~Opioids|~~opioid]] substance of the [[~~Substituted piperidines|~~piperidine]] class. It is ~~used~~ to treat severe pain (~~like~~ cancer pain, postoperative pain, gallstone pain, and kidney pain).

'''Ketobemidone''' (also known by the brand names '''Ketogan''', and '''Ketorax''') is an [[psychoactive class::opioid]] substance of the [[chemical class::piperidine]] class. It belongs to a group of synthetic opioids. The mechanism of action involves [[agonist|binding activity]] at [[opioid]] [[receptors]].

It is commonly prescribed to treat severe pain (i.e. cancer pain, postoperative pain, gallstone pain, and kidney pain). It is marketed in Denmark, Iceland, Norway and Sweden for this purpose.<ref>Brayfield A, ed. (9 January 2017). "Ketobemidone Hydrochloride: Martindale: The Complete Drug Reference". ''MedicinesComplete''. London, UK: Pharmaceutical Press.</ref>

[[Subjective effects]] include [[sedation]], [[pain relief]], [[muscle relaxation]], [[compulsive redosing]], and [[euphoria]]. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted, in part, by its metabolite norketobemidone.<ref>Ebert B, Thorkildsen C, Andersen S, Christrup LL, Hjeds H (September 1998). "Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists". ''Biochemical Pharmacology''. '''56''' (5): 553–9. doi:10.1016/S0006-2952(98)00088-4. <nowiki>PMID 9783723</nowiki>.</ref>

It has high abuse potential comparable to that of [[morphine]]. Chronic use is associated with psychological dependence and addiction. It is highly advised to use harm reduction practices if using this substance.

==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}}

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==Chemistry==

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==

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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.

~~<br />~~

==Subjective effects==

{{effects/base

|{{effects/physical|

*'''[[Effect::Sedation]]'''

*'''[[Effect::Dizziness]]'''

*'''[[Effect::Headache]]'''

*'''[[Effect::Bradycardia]]'''

*'''[[Effect::Physical euphoria]]'''

*'''[[Effect::Constipation]]'''

*'''[[Effect::Difficulty urinating]]'''

*'''[[Effect::Nausea]]'''

*'''[[Effect::Vomiting]]'''

*'''[[Effect::Pain relief]]'''

*'''[[Effect::Pupil constriction]]'''

*'''[[Effect::Itchiness]]'''

*'''[[Effect::Respiratory depression]]'''

*'''[[Effect::Decreased blood pressure]]'''

*'''[[Effect::Dry mouth]]'''

}}

|{{effects/cognitive|

*'''[[Effect::Cognitive euphoria]]'''

*'''[[Effect::Anxiety suppression]]'''

*'''[[Effect::Confusion]]'''

*'''[[Effect::Irritability]]''' - While opioids are well known for their ability to improve mood, they can also have the paradoxical effect of increasing the user's sensitivity to irritable stimuli. This can manifest as aloofness and sudden outbursts of anger and aggression (colloquially known as "opiate rage"). It appears to occur more frequently during the comedown of the experience and/or with heavy use.

}}

{{effects/disconnective|

Ketobemidone is thought to have disconnective effects due to its affinity for the [[NMDA_receptor_antagonist|NMDA]] receptor.

*'''[[Effect::Cognitive disconnection]]'''

*'''[[Effect::Physical disconnection]]'''

}}

{{effects/visual|

====Suppressions====

*'''[[Effect::Double vision]]''' - At high doses, the eyes unfocus and re-focus uncontrollably. This creates a blurred effect and double vision that is present no matter where one focuses their eyes. This can be so intense it becomes impossible to read or drive.

*'''[[Effect::Acuity suppression]]'''

====Hallucinatory States====

*'''[[Effect::Internal hallucination]]''' - One may experience a state of semi-consciousness and [[hypnagogia]] during heavy dosage nodding which results in dream-like states and up to level 3 [[Lucid_dreaming#Internally_sourced_sensory_input|imagery]]. This is often accompanied by ill-defined [[geometry]].

}}

===Experience reports===

Anecdotal reports which describe the effects of this compound within our [[experience index]] include:

{{#ask: [[Category:Ketobemidone]][[Category:Experience]]|format=ul|Columns=1}}

Additional experience reports can be found here:

*~~Euphoria~~

*[https://www.erowid.org/experiences/subs/exp_Ketobemidone.shtml Erowid Experience Vaults: Ketobemidone]

*Confusion

*Sedation

*Dizziness

*Headache

*Blurred vision

*Bradycardia

*Respiratory depression

*Dry mouth

*Nausea

*Vomiting

*Constipation

*Difficulty urinating

*Decreased blood pressure

==Toxicity and harm potential==

===~~Tolerance~~ and ~~addiction~~ potential===

===Dependence and abuse potential===

===Dangerous interactions===

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==Legal status==

*'''Australia:''' S9 (Prohibited substance)

*'''Australia:''' S9 (Prohibited substance).{{citation needed}}

*'''Canada:''' Schedule I

*'''Canada:''' Schedule I.{{citation needed}}

*'''Germany:''' Anlage II (Authorized trade only, not prescriptible)

*'''Germany:''' Anlage II (Authorized trade only, not prescriptible).{{citation needed}}

*'''United States:''' Schedule I

*'''United States:''' Ketobemidone is a Schedule I substance.{{citation needed}}

*'''European Union:''' ~~Prescription~~ only<ref>https://www.ema.europa.eu/en/documents/psusa/ketobemidone-list-nationally-authorised-medicinal-products-psusa/0001807/202005_en.pdf</ref>

*'''European Union:''' Available by prescription only<ref>https://www.ema.europa.eu/en/documents/psusa/ketobemidone-list-nationally-authorised-medicinal-products-psusa/0001807/202005_en.pdf</ref>

==See also==

@@ Line 1: / Line 1: @@
-{{headerpanel|{{DepressantOD|opiates}}}}
+{{headerpanel|{{DepressantOD|opiates}}{{approval}}}}
-{{stub}}
 {{SummarySheet}}
 {{SubstanceBox/Ketobemidone}}
-'''Ketobemidone''' (also known by the brand names '''Ketogan''', and '''Ketorax''') is a synthetic [[Opioids|opioid]] substance of the [[Substituted piperidines|piperidine]] class. It is used to treat severe pain (like cancer pain, postoperative pain, gallstone pain, and kidney pain).
+'''Ketobemidone''' (also known by the brand names '''Ketogan''', and '''Ketorax''') is an [[psychoactive class::opioid]] substance of the [[chemical class::piperidine]] class. It belongs to a group of synthetic opioids. The mechanism of action involves [[agonist|binding activity]] at [[opioid]] [[receptors]].
+It is commonly prescribed to treat severe pain (i.e. cancer pain, postoperative pain, gallstone pain, and kidney pain). It is marketed in Denmark, Iceland, Norway and Sweden for this purpose.<ref>Brayfield A, ed. (9 January 2017). "Ketobemidone Hydrochloride: Martindale: The Complete Drug Reference". ''MedicinesComplete''. London, UK: Pharmaceutical Press.</ref>
+[[Subjective effects]] include [[sedation]], [[pain relief]], [[muscle relaxation]], [[compulsive redosing]], and [[euphoria]]. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted, in part, by its metabolite norketobemidone.<ref>Ebert B, Thorkildsen C, Andersen S, Christrup LL, Hjeds H (September 1998). "Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists". ''Biochemical Pharmacology''. '''56''' (5): 553–9. doi:10.1016/S0006-2952(98)00088-4. <nowiki>PMID 9783723</nowiki>.</ref>
+It has high abuse potential comparable to that of [[morphine]]. Chronic use is associated with psychological dependence and addiction. It is highly advised to use harm reduction practices if using this substance.
 ==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 13: / Line 18: @@
 ==Chemistry==
+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==
@@ Line 18: / Line 26: @@
 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.
-<br />
 ==Subjective effects==
+{{effectStub}}
+{{Preamble/SubjectiveEffects}}
+{{effects/base
+|{{effects/physical|
+*'''[[Effect::Sedation]]'''
+*'''[[Effect::Dizziness]]'''
+*'''[[Effect::Headache]]'''
+*'''[[Effect::Bradycardia]]'''
+*'''[[Effect::Physical euphoria]]'''
+*'''[[Effect::Constipation]]'''
+*'''[[Effect::Difficulty urinating]]'''
+*'''[[Effect::Nausea]]'''
+*'''[[Effect::Vomiting]]'''
+*'''[[Effect::Pain relief]]'''
+*'''[[Effect::Pupil constriction]]'''
+*'''[[Effect::Itchiness]]'''
+*'''[[Effect::Respiratory depression]]'''
+*'''[[Effect::Decreased blood pressure]]'''
+*'''[[Effect::Dry mouth]]'''
+}}
+|{{effects/cognitive|
+*'''[[Effect::Cognitive euphoria]]'''
+*'''[[Effect::Anxiety suppression]]'''
+*'''[[Effect::Confusion]]'''
+*'''[[Effect::Irritability]]''' - While opioids are well known for their ability to improve mood, they can also have the paradoxical effect of increasing the user's sensitivity to irritable stimuli. This can manifest as aloofness and sudden outbursts of anger and aggression (colloquially known as "opiate rage"). It appears to occur more frequently during the comedown of the experience and/or with heavy use.
+}}
+{{effects/disconnective|
+Ketobemidone is thought to have disconnective effects due to its affinity for the [[NMDA_receptor_antagonist|NMDA]] receptor.
+*'''[[Effect::Cognitive disconnection]]'''
+*'''[[Effect::Physical disconnection]]'''
+}}
+{{effects/visual|
+====Suppressions====
+*'''[[Effect::Double vision]]''' - At high doses, the eyes unfocus and re-focus uncontrollably. This creates a blurred effect and double vision that is present no matter where one focuses their eyes. This can be so intense it becomes impossible to read or drive.
+*'''[[Effect::Acuity suppression]]'''
+====Hallucinatory States====
+*'''[[Effect::Internal hallucination]]''' - One may experience a state of semi-consciousness and [[hypnagogia]] during heavy dosage nodding which results in dream-like states and up to level 3 [[Lucid_dreaming#Internally_sourced_sensory_input|imagery]]. This is often accompanied by ill-defined [[geometry]].
+}}
+}}
+===Experience reports===
+Anecdotal reports which describe the effects of this compound within our [[experience index]] include:
+{{#ask: [[Category:Ketobemidone]][[Category:Experience]]|format=ul|Columns=1}}
+Additional experience reports can be found here:
-*Euphoria
+*[https://www.erowid.org/experiences/subs/exp_Ketobemidone.shtml Erowid Experience Vaults: Ketobemidone]
-*Confusion
-*Sedation
-*Dizziness
-*Headache
-*Blurred vision
-*Bradycardia
-*Respiratory depression
-*Dry mouth
-*Nausea
-*Vomiting
-*Constipation
-*Difficulty urinating
-*Decreased blood pressure
 ==Toxicity and harm potential==
+{{toxicityStub}}
-===Tolerance and addiction potential===
+===Dependence and abuse potential===
 ===Dangerous interactions===
@@ Line 50: / Line 96: @@
 ==Legal status==
+{{legalStub}}
-*'''Australia:''' S9 (Prohibited substance)
+*'''Australia:''' S9 (Prohibited substance).{{citation needed}}
-*'''Canada:''' Schedule I
+*'''Canada:''' Schedule I.{{citation needed}}
-*'''Germany:''' Anlage II (Authorized trade only, not prescriptible)
+*'''Germany:''' Anlage II (Authorized trade only, not prescriptible).{{citation needed}}
-*'''United States:''' Schedule I
+*'''United States:''' Ketobemidone is a Schedule I substance.{{citation needed}}
-*'''European Union:''' Prescription only<ref>https://www.ema.europa.eu/en/documents/psusa/ketobemidone-list-nationally-authorised-medicinal-products-psusa/0001807/202005_en.pdf</ref>
+*'''European Union:''' Available by prescription only<ref>https://www.ema.europa.eu/en/documents/psusa/ketobemidone-list-nationally-authorised-medicinal-products-psusa/0001807/202005_en.pdf</ref>
 ==See also==