Jump to content

Benperidol: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
rv vandalism
Added Pharmacology
Line 1: Line 1:
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 459533587
| verifiedrevid = 459533587
| IUPAC_name = 1-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}-1,3-dihydro-2''H''-benzimidazol-2-one
| IUPAC_name = 1-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}-1,3-dihydro-2''H''-benzimidazol-2-one
| image = Benperidol.svg
| image = Benperidol.svg
| alt = Skeletal formula of benperidol
| alt = Skeletal formula of benperidol
| width = 240
| width = 240
| image2 = Benperidol 3D ball.png
| image2 = Benperidol 3D ball.png
| alt2 = Ball-and-stick model of the benperidol molecule
| alt2 = Ball-and-stick model of the benperidol molecule
| width2 = 250
| width2 = 250


<!--Clinical data-->
<!--Clinical data-->| tradename = Anquil, Frenactil
⚫
| Drugs.com = {{drugs.com|international|benperidol}}
| tradename = Anquil, Frenactil
⚫
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫
| Drugs.com = {{drugs.com|international|benperidol}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
⚫
| pregnancy_category =
⚫
| pregnancy_US = <!-- A / B / C / D / X -->
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
⚫
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = Rx-only
⚫
| legal_status =
| legal_US = Rx-only
⚫
| legal_status =
| routes_of_administration = Oral
| routes_of_administration = Oral


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->| bioavailability =
⚫
| protein_bound =
| bioavailability =
⚫
| metabolism =
⚫
| protein_bound =
⚫
| elimination_half-life = 8 hours
⚫
| metabolism =
⚫
| excretion = <!--Identifiers-->
⚫
| elimination_half-life =
⚫
| CAS_number_Ref = {{cascite|changed|??}}
| excretion =
⚫
| CAS_number = 2062-84-2
⚫
| ATC_prefix = N05
⚫
| ATC_suffix = AD07
⚫
| PubChem = 16363
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
⚫
| DrugBank =
⚫
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
⚫
| ChemSpiderID = 15521
⚫
| UNII_Ref = {{fdacite|correct|FDA}}
⚫
| UNII = 97O6X78C53
⚫
| ChEMBL_Ref = {{ebicite|correct|EBI}}
⚫
| ChEMBL = 297302


⚫
<!--Chemical data-->| C = 22
⚫
<!--Identifiers-->
| H = 24
⚫
| CAS_number_Ref = {{cascite|changed|??}}
| F = 1
⚫
| CAS_number = 2062-84-2
| N = 3
⚫
| ATC_prefix = N05
| O = 2
⚫
| ATC_suffix = AD07
⚫
| smiles = Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4
⚫
| PubChem = 16363
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
⚫
| StdInChI = 1S/C22H24FN3O2/c23-17-9-7-16(8-10-17)21(27)6-3-13-25-14-11-18(12-15-25)26-20-5-2-1-4-19(20)24-22(26)28/h1-2,4-5,7-10,18H,3,6,11-15H2,(H,24,28)
⚫
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
⚫
| StdInChIKey = FEBOTPHFXYHVPL-UHFFFAOYSA-N
⚫
| ChemSpiderID = 15521
| drug_name =
⚫
| UNII_Ref = {{fdacite|correct|FDA}}
| caption =
⚫
| UNII = 97O6X78C53
| type =
⚫
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| MedlinePlus =
⚫
| ChEMBL = 297302
| licence_EU =

| licence_US =
⚫
<!--Chemical data-->
}}
| C=22 | H=24
| F=1 | N=3
| O=2
⚫
| smiles = Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4
⚫
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
⚫
| StdInChI = 1S/C22H24FN3O2/c23-17-9-7-16(8-10-17)21(27)6-3-13-25-14-11-18(12-15-25)26-20-5-2-1-4-19(20)24-22(26)28/h1-2,4-5,7-10,18H,3,6,11-15H2,(H,24,28)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
⚫
| StdInChIKey = FEBOTPHFXYHVPL-UHFFFAOYSA-N
|drug_name=|caption=|type=|MedlinePlus=|licence_EU=|licence_US=}}


'''Benperidol''', sold under the trade name '''Anquil'''<ref>{{Cite journal | vauthors = Council A, Kuenssberg V |date=1974-02-01|title=Benperidol - a drug for sexual offenders?|journal=Drug and Therapeutics Bulletin|publisher=BMJ Publishing Group Ltd|volume=12|issue=3|pages=12|doi=10.1136/dtb.12.3.12|pmid=4457302|s2cid=44581451}}</ref> among others, is a drug which is a highly potent [[butyrophenone]] derivative. It is the most potent neuroleptic on the European market, with [[chlorpromazine]] equivalency as high as 75 to 100 (about 150 to 200% potency in terms of dose compared to [[haloperidol]]).<ref>{{cite book | vauthors = Möller HJ, Müller WE, Bandelow | title = Neuroleptika: pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen; mit 136 Tabellen. | publisher = Wiss. Verlag-Ges. | date = 2001 | language = de | isbn = 3-8047-1773-X }}</ref> It is an [[antipsychotic]], which can be used for the treatment of [[schizophrenia]],<ref name="pmid14092279">{{cite journal | vauthors = Bobon J, Collard J, Lecoq R | title = [Benperidol and promazine: a "double blind" comparative study in mental geriatrics] | language = fr | journal = Acta Neurologica et Psychiatrica Belgica | volume = 63 | pages = 839–43 | date = October 1963 | pmid = 14092279 }}</ref> but it is primarily used to control [[hypersexuality]] syndromes<ref>British National Formulary (49th), British Medical Association 2005 p 183</ref> and is sometimes prescribed to [[sex offender]]s as a condition of their [[parole]], as an alternative to anti-[[androgen]] drugs such as [[cyproterone acetate]].<ref name="pmid1107462">{{cite journal | vauthors = Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ | title = Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers | journal = The Journal of Endocrinology | volume = 67 | issue = 2 | pages = 179–88 | date = November 1975 | pmid = 1107462 | doi = 10.1677/joe.0.0670179 }}</ref>
'''Benperidol''', sold under the trade name '''Anquil'''<ref>{{Cite journal | vauthors = Council A, Kuenssberg V |date=1974-02-01|title=Benperidol - a drug for sexual offenders?|journal=Drug and Therapeutics Bulletin|publisher=BMJ Publishing Group Ltd|volume=12|issue=3|pages=12|doi=10.1136/dtb.12.3.12|pmid=4457302|s2cid=44581451}}</ref> among others, is a drug which is a highly potent [[butyrophenone]] derivative. It is the most potent neuroleptic on the European market, with [[chlorpromazine]] equivalency as high as 75 to 100 (about 150 to 200% potency in terms of dose compared to [[haloperidol]]).<ref>{{cite book | vauthors = Möller HJ, Müller WE, Bandelow | title = Neuroleptika: pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen; mit 136 Tabellen. | publisher = Wiss. Verlag-Ges. | date = 2001 | language = de | isbn = 3-8047-1773-X }}</ref> It is an [[antipsychotic]], which can be used for the treatment of [[schizophrenia]],<ref name="pmid14092279">{{cite journal | vauthors = Bobon J, Collard J, Lecoq R | title = [Benperidol and promazine: a "double blind" comparative study in mental geriatrics] | language = fr | journal = Acta Neurologica et Psychiatrica Belgica | volume = 63 | pages = 839–43 | date = October 1963 | pmid = 14092279 }}</ref> but it is primarily used to control [[hypersexuality]] syndromes<ref>British National Formulary (49th), British Medical Association 2005 p 183</ref> and is sometimes prescribed to [[sex offender]]s as a condition of their [[parole]], as an alternative to anti-[[androgen]] drugs such as [[cyproterone acetate]].<ref name="pmid1107462">{{cite journal | vauthors = Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ | title = Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers | journal = The Journal of Endocrinology | volume = 67 | issue = 2 | pages = 179–88 | date = November 1975 | pmid = 1107462 | doi = 10.1677/joe.0.0670179 }}</ref>


Benperidol was discovered at [[Janssen Pharmaceutica]] in 1961.
Benperidol was discovered at [[Janssen Pharmaceutica]] in 1961.

== Pharmacology ==

=== Pharmacodynamics ===
Benperidol is a strong [[dopamine]] [[receptor antagonist]] ([[Dopamine receptor D2|D2]] (''K''<sub>i</sub> 0.027 nM) and [[Dopamine receptor D4|D4]] (''K''<sub>i</sub> 0.066 nM))<ref name=":1" /> with weaker [[serotonin]] receptor antagonism ([[5-HT2A receptor|5-HT<sub>2A</sub>]] (''K''<sub>i</sub> 3.75 nM))<ref name=":1" />. In high doses it has antihistaminergic and alpha-adrenergic properties. It's anticholinergic effects are minimal.<ref name=":0">{{Cite journal |last=Schwarz |first=Christian |last2=Hartung |first2=Benno |last3=Leucht |first3=Stefan |date=2005-04-20 |title=Benperidol for schizophrenia |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017029/ |journal=The Cochrane Database of Systematic Reviews |volume=2005 |issue=2 |pages=CD003083 |doi=10.1002/14651858.CD003083.pub2 |issn=1469-493X |pmc=7017029 |pmid=15846648}}</ref>
{| class="wikitable"
|+Benperidol<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 11 March 2022 | url = https://pdsp.unc.edu/databases/pdsp.php?recDDRadio=recDDRadio&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Benperidol&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>
! Site !! K<sub>i</sub> (nM) !! Action !! Ref
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 3.75 || Antagonist ||<ref name=":1">{{Cite journal |last=Li |first=Peng |last2=Snyder |first2=Gretchen L. |last3=Vanover |first3=Kimberly E. |date=December 2016 |title=Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, 
Present and Future |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112764/ |journal=Current Topics in Medicinal Chemistry |volume=16 |issue=29 |pages=3385–3403 |doi=10.2174/1568026616666160608084834 |issn=1568-0266 |pmc=5112764 |pmid=27291902}}</ref>
|-
| [[Dopamine D2 receptor|D<sub>2</sub>]] || 0.027 || Antagonist ||<ref name=":1" />
|-
| [[Dopamine D4 receptor|D<sub>4</sub>]] || 0.06 || Antagonist ||<ref name=":1" />
|}

=== Pharmacokinetics ===
Benperidol is absorbed well and undergoes extensive [[First pass effect|first pass metabolism]]. One percent of benperidol is excreted in urine. The half-life of benperidol is 8 hours.<ref name=":0" />


==Synthesis==
==Synthesis==
[[File:Benperidol synthesis.svg|thumb|center|500px|Benperidol synthesis:<ref>{{Cite patent|country=BE|number=626307}} (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to {{cite patent|country=GB|number=989755|pubdate=1965-04-22|title=1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds|assign1=[[Janssen_Pharmaceuticals#History|N.V. Research Laboratorium Dr. C. Janssen]]}}.</ref>]]
[[File:Benperidol synthesis.svg|thumb|center|500px|Benperidol synthesis:<ref name=":2">{{Cite patent|country=BE|number=626307}} (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to {{cite patent|country=GB|number=989755|pubdate=1965-04-22|title=1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds|assign1=[[Janssen_Pharmaceuticals#History|N.V. Research Laboratorium Dr. C. Janssen]]}}.</ref>]]
==See also==
==See also==
*[[Timiperone]] has the same structure but thiourea instead of normal urea.
*[[Timiperone]] has the same structure but thiourea instead of normal urea.

Revision as of 15:20, 10 March 2022

Benperidol
Skeletal formula of benperidol
Ball-and-stick model of the benperidol molecule
Clinical data
Trade namesAnquil, Frenactil
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life8 hours
Identifiers
  • 1-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.016.521 Edit this at Wikidata
Chemical and physical data
FormulaC22H24FN3O2
Molar mass381.451 g·mol−1
3D model (JSmol)
  • Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4
  • InChI=1S/C22H24FN3O2/c23-17-9-7-16(8-10-17)21(27)6-3-13-25-14-11-18(12-15-25)26-20-5-2-1-4-19(20)24-22(26)28/h1-2,4-5,7-10,18H,3,6,11-15H2,(H,24,28) checkY
  • Key:FEBOTPHFXYHVPL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Benperidol, sold under the trade name Anquil[1] among others, is a drug which is a highly potent butyrophenone derivative. It is the most potent neuroleptic on the European market, with chlorpromazine equivalency as high as 75 to 100 (about 150 to 200% potency in terms of dose compared to haloperidol).[2] It is an antipsychotic, which can be used for the treatment of schizophrenia,[3] but it is primarily used to control hypersexuality syndromes[4] and is sometimes prescribed to sex offenders as a condition of their parole, as an alternative to anti-androgen drugs such as cyproterone acetate.[5]

Benperidol was discovered at Janssen Pharmaceutica in 1961.

Pharmacology

Pharmacodynamics

Benperidol is a strong dopamine receptor antagonist (D2 (Ki 0.027 nM) and D4 (Ki 0.066 nM))[6] with weaker serotonin receptor antagonism (5-HT2A (Ki 3.75 nM))[6]. In high doses it has antihistaminergic and alpha-adrenergic properties. It's anticholinergic effects are minimal.[7]

Benperidol[8]
Site Ki (nM) Action Ref
5-HT2A 3.75 Antagonist [6]
D2 0.027 Antagonist [6]
D4 0.06 Antagonist [6]

Pharmacokinetics

Benperidol is absorbed well and undergoes extensive first pass metabolism. One percent of benperidol is excreted in urine. The half-life of benperidol is 8 hours.[7]

Synthesis

Benperidol synthesis:[9]

See also

References

  1. ^ Council A, Kuenssberg V (1974-02-01). "Benperidol - a drug for sexual offenders?". Drug and Therapeutics Bulletin. 12 (3). BMJ Publishing Group Ltd: 12. doi:10.1136/dtb.12.3.12. PMID 4457302. S2CID 44581451.
  2. ^ Möller HJ, Müller WE, Bandelow (2001). Neuroleptika: pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen; mit 136 Tabellen (in German). Wiss. Verlag-Ges. ISBN 3-8047-1773-X.
  3. ^ Bobon J, Collard J, Lecoq R (October 1963). "[Benperidol and promazine: a "double blind" comparative study in mental geriatrics]". Acta Neurologica et Psychiatrica Belgica (in French). 63: 839–43. PMID 14092279.
  4. ^ British National Formulary (49th), British Medical Association 2005 p 183
  5. ^ Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ (November 1975). "Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers". The Journal of Endocrinology. 67 (2): 179–88. doi:10.1677/joe.0.0670179. PMID 1107462.
  6. ^ a b c d e Li, Peng; Snyder, Gretchen L.; Vanover, Kimberly E. (December 2016). "Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, 
Present and Future". Current Topics in Medicinal Chemistry. 16 (29): 3385–3403. doi:10.2174/1568026616666160608084834. ISSN 1568-0266. PMC 5112764. PMID 27291902.
  7. ^ a b Schwarz, Christian; Hartung, Benno; Leucht, Stefan (2005-04-20). "Benperidol for schizophrenia". The Cochrane Database of Systematic Reviews. 2005 (2): CD003083. doi:10.1002/14651858.CD003083.pub2. ISSN 1469-493X. PMC 7017029. PMID 15846648.
  8. ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 11 March 2022.
  9. ^ BE 626307  (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to GB 989755, "1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds", published 1965-04-22, assigned to N.V. Research Laboratorium Dr. C. Janssen .
Stub icon

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Benperidol&oldid=1076330177"