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{{Short description|Typical antipsychotic medication}}
{{Drugbox
{{Infobox drug
| 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
| tradename = Anquil, Frenactil
| Drugs.com = {{drugs.com|international|benperidol}}
| Drugs.com = {{drugs.com|international|benperidol}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| pregnancy_category =
| legal_AU = [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 4|S4]] (Prescription only)
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = Rx-only
| legal_US = Rx-only
| legal_status =
| legal_status =
| routes_of_administration = Oral
| routes_of_administration = Oral


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism =
| metabolism =
| elimination_half-life =
| elimination_half-life = 8 hours
| excretion =
| excretion = <!--Identifiers-->
⚫
| CAS_number_Ref = {{cascite|changed|??}}

⚫
| CAS_number = 2062-84-2
<!--Identifiers-->
⚫
| ATC_prefix = N05
⚫
| CAS_number_Ref = {{cascite|changed|??}}
⚫
| ATC_suffix = AD07
⚫
| CAS_number = 983-42-6
⚫
| PubChem = 16363
⚫
| ATC_prefix = N05
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
⚫
| ATC_suffix = AD07
⚫
| DrugBank = DB12867
⚫
| PubChem = 16363
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
⚫
| ChemSpiderID = 15521
⚫
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII_Ref = {{fdacite|correct|FDA}}
⚫
| UNII = 97O6X78C53
⚫
| ChemSpiderID = 15521
| UNII_Ref = {{fdacite|correct|FDA}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
⚫
| ChEMBL = 297302
⚫
| UNII = 97O6X78C53
| KEGG = D02627
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEBI = 93403
⚫
| ChEMBL = 297302


<!--Chemical data-->
<!--Chemical data-->
| C=22 | H=24
| C = 22
| H = 24
| F=1 | N=3
| F = 1
| O=2
| N = 3
| molecular_weight = 381.443 g/mol
| O = 2
| smiles = Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4
| smiles = Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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)
| 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_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FEBOTPHFXYHVPL-UHFFFAOYSA-N
| StdInChIKey = FEBOTPHFXYHVPL-UHFFFAOYSA-N
|drug_name=|caption=|type=|MedlinePlus=|licence_EU=|licence_US=}}
| drug_name =
| caption =
| type =
| MedlinePlus =
| licence_EU =
| licence_US =
}}


'''Benperidol''', sold under the trade name '''Anquil'''<ref>{{Cite journal|last=|first=|date=1974-02-01|title=Benperidol - a drug for sexual offenders?|url=|journal=Drug and Therapeutics Bulletin|publisher=BMJ Publishing Group Ltd|volume=12|pages=12|via=}}</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>Möller; Müller; Bandelow: Neuroleptika, 2001, WVG; {{ISBN|3-8047-1773-X}} (in German)</ref> It is an [[antipsychotic]], which can be used for the treatment of [[schizophrenia]],<ref>Bobon J, Collard J, Lecoq R, Benperidol and promazine: a "double blind" comparative study in mental geriatrics, Acta Neurol Belg. 1963 Oct;63:839-43.</ref> but it is primarily used to control [[Anti-social behaviour|antisocial]] [[hypersexual]] behaviour,<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>Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ., Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers, Journal of Endocrinology. 1975 Nov;67(2):179-88.</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 [[typical antipsychotic]] primarily used to treat [[hypersexuality]] syndromes<ref>British National Formulary (49th), British Medical Association 2005 p 183</ref> and can be used to treat [[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> It is a highly potent [[butyrophenone]] derivative and is the most potent neuroleptic in the European market, with [[chlorpromazine]] equivalency as high as 75 to 100 (about 150 to 200% the potency per dose of [[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 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 by [[Janssen Pharmaceutica]] in 1961 and has been marketed since 1966. It is mainly used in [[Germany]], but it is also available in [[Belgium]], [[Greece]], [[Italy]], the [[Netherlands]], and the [[United Kingdom]].<ref>{{Cite web | title = NCATS Inxight Drugs — BENPERIDOL | access-date = 13 March 2022 | url = https://drugs.ncats.io/drug/97O6X78C53}}</ref>
Benperidol was discovered at [[Janssen Pharmaceutica]] in 1961.

== Pharmacology ==

=== Pharmacodynamics ===
Benperidol is a strong [[dopamine]] [[receptor antagonist]] ([[Dopamine receptor D2|D<sub>2</sub>]] (''K''<sub>i</sub> 0.027 nM) and [[Dopamine receptor D4|D<sub>4</sub>]] (''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 possesses minimal anticholinergic properties.<ref name=":0">{{cite journal | vauthors = Leucht S, Hartung B | title = Benperidol for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2005 | issue = 2 | pages = CD003083 | date = April 2005 | pmid = 15846648 | pmc = 7017029 | doi = 10.1002/14651858.CD003083.pub2 }}</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 | vauthors = Li P, Snyder GL, Vanover KE | title = Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future | journal = Current Topics in Medicinal Chemistry | volume = 16 | issue = 29 | pages = 3385–3403 | date = December 2016 | pmid = 27291902 | pmc = 5112764 | doi = 10.2174/1568026616666160608084834 }}</ref>
|-
| [[Dopamine D1 receptor|D<sub>1</sub>]] || 4,100 || Antagonist ||<ref name=":1" />
|-
| [[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==
4-(2-Keto-1-benzimidazolinyl)piperidine ('''1''') is alkylated with 4-chloro-4'-Fluorobutyrophenone ('''2''') to produce benperidol ('''3''').<ref>[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-02-0036 Thieme]</ref><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>
[[File:Benperidol synthesis.svg|thumb|center|500px|Benperidol synthesis:<ref>{{Cite patent|BE|626307}} (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to {{cite patent|GB|989755}}.</ref>]]
[[File:Benperidol synthesis.svg|thumb|center|501px|]]

==See also==
==See also==
*[[Timiperone]] has the same structure but thiourea instead of normal urea.
*[[Timiperone]] has a similar [[chemical structure]] with a [[thiourea]] [[Functional group|group]] instead of a [[urea]] group.
*[[Pimozide]] & [[Oxiperomide]] & [[Neflumozide]] are also made from 4-(1-Benzimidazolinone)piperidine prec.
*[[Pimozide]], [[bezitramide]], [[oxiperomide]], and [[neflumozide]]) are also made from 4-(1-benzimidazolinone)piperidine precursor
*[[Droperidol]] is self-same albeit with a [[Wikt:tetrahydropyridine|tetrahydropyridine]] ring.
*[[Droperidol]] is similar, but has a [[Wikt:tetrahydropyridine|tetrahydropyridine]] ring.


== References ==
== References ==
Line 77: Line 107:
[[Category:Butyrophenone antipsychotics]]
[[Category:Butyrophenone antipsychotics]]
[[Category:Janssen Pharmaceutica]]
[[Category:Janssen Pharmaceutica]]
[[Category:Fluoroarenes]]
[[Category:4-Fluorophenyl compounds]]
[[Category:Piperidines]]
[[Category:Piperidines]]
[[Category:Typical antipsychotics]]
[[Category:Typical antipsychotics]]

{{nervous-system-drug-stub}}

Latest revision as of 20:54, 4 September 2024

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
DrugBank
ChemSpider
UNII
KEGG
ChEBI
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 typical antipsychotic primarily used to treat hypersexuality syndromes[2] and can be used to treat schizophrenia.[3] It is a highly potent butyrophenone derivative and is the most potent neuroleptic in the European market, with chlorpromazine equivalency as high as 75 to 100 (about 150 to 200% the potency per dose of haloperidol).[4] It 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 by Janssen Pharmaceutica in 1961 and has been marketed since 1966. It is mainly used in Germany, but it is also available in Belgium, Greece, Italy, the Netherlands, and the United Kingdom.[6]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Benperidol is a strong dopamine receptor antagonist (D2 (Ki 0.027 nM) and D4 (Ki 0.066 nM))[7] with weaker serotonin receptor antagonism (5-HT2A (Ki 3.75 nM)).[7] In high doses, it has antihistaminergic and alpha-adrenergic properties. It possesses minimal anticholinergic properties.[8]

Benperidol[9]
Site Ki (nM) Action Ref
5-HT2A 3.75 Antagonist [7]
D1 4,100 Antagonist [7]
D2 0.027 Antagonist [7]
D4 0.06 Antagonist [7]

Pharmacokinetics

[edit]

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.[8]

Synthesis

[edit]

4-(2-Keto-1-benzimidazolinyl)piperidine (1) is alkylated with 4-chloro-4'-Fluorobutyrophenone (2) to produce benperidol (3).[10][11]

See also

[edit]

References

[edit]
  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. ^ British National Formulary (49th), British Medical Association 2005 p 183
  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. ^ 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.
  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. ^ "NCATS Inxight Drugs — BENPERIDOL". Retrieved 13 March 2022.
  7. ^ a b c d e f Li P, Snyder GL, Vanover KE (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. PMC 5112764. PMID 27291902.
  8. ^ a b Leucht S, Hartung B (April 2005). "Benperidol for schizophrenia". The Cochrane Database of Systematic Reviews. 2005 (2): CD003083. doi:10.1002/14651858.CD003083.pub2. PMC 7017029. PMID 15846648.
  9. ^ 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.
  10. ^ Thieme
  11. ^ 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 
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Benperidol&oldid=1244061653"