Benperidol: Difference between revisions

{{Short description|Typical antipsychotic medication}}

{{Infobox drug

| Verifiedfields = changed

| verifiedrevid = 459533587

| IUPAC_name = 1-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}-1,3-dihydro-2''H''-benzimidazol-2-one

| image = Benperidol.svg

| alt = Skeletal formula of benperidol

| width = 240

| image2 = Benperidol 3D ball.png

| alt2 = Ball-and-stick model of the benperidol molecule

| width2 = 250

| tradename = Anquil, Frenactil

| Drugs.com = {{drugs.com|international|benperidol}}

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_US = <!-- A / B / C / D / X -->

| pregnancy_category =

| legal_AU = [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 4|S4]] (Prescription only)

| legal_UK = <!-- GSL / P / POM / CD -->

| legal_US = Rx-only

| legal_status =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life = 8 hours

| excretion = <!--Identifiers-->

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 2062-84-2

| ATC_prefix = N05

| ATC_suffix = AD07

| PubChem = 16363

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB12867

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 15521

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 97O6X78C53

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 297302

| KEGG = D02627

| ChEBI = 93403

| 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 [[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>

== Pharmacology ==

=== Pharmacodynamics ===

Benperidol is a strong [[dopamine]] [[receptor antagonist]] ([[Dopamine receptor D2|D₂]] (''K''_i 0.027 nM) and [[Dopamine receptor D4|D₄]] (''K''_i 0.066 nM))<ref name=":1" /> with weaker [[serotonin]] receptor antagonism ([[5-HT2A receptor|5-HT_2A]] (''K''_i 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_i 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_i (nM) !! Action !! Ref

|-

| [[5-HT2A receptor|5-HT_2A]] || 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|D₁]] || 4,100 || Antagonist ||<ref name=":1" />

|-

| [[Dopamine D2 receptor|D₂]] || 0.027 || Antagonist ||<ref name=":1" />

|-

| [[Dopamine D4 receptor|D₄]] || 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==

[[File:Benperidol synthesis.svg|thumb|center|501px|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-02-0036 Thieme] Patent:<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>]]

4-(2-Keto-1-benzimidazolinyl)piperidine [20662-53-7] ('''1''') is alkylated with 4-Chloro-4'-Fluorobutyrophenone [3874-54-2] ('''2''').

==See also==

*[[Timiperone]] has a similar [[chemical structure]] with a [[thiourea]] [[Functional group|group]] instead of a [[urea]] group.

*[[Pimozide]] & [[Bezitramide]] (& [[Oxiperomide]] & [[Neflumozide]]) are also made from 4-(1-Benzimidazolinone)piperidine precursor

*[[Droperidol]] is similar, but has a [[Wikt:tetrahydropyridine|tetrahydropyridine]] ring.

[[Category:Belgian inventions]]

[[Category:Fluoroarenes]]

[[Category:Piperidines]]

[[Category:Typical antipsychotics]]