Benperidol

Benperidol

Clinical data
Trade names	Anquil, Frenactil
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	N05AD07 ( WHO )
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Elimination half-life	8 hours
Identifiers
IUPAC name 1-{1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
CAS Number	2062-84-2  N
PubChem CID	16363
DrugBank	DB12867  Y
ChemSpider	15521  Y
UNII	97O6X78C53
KEGG	D02627
ChEBI	CHEBI:93403
ChEMBL	ChEMBL297302  Y
CompTox Dashboard (EPA)	DTXSID7045364
ECHA InfoCard	100.016.521
Chemical and physical data
Formula	C22H24FN3O2
Molar mass	381.451 g·mol−1
3D model (JSmol)	Interactive image
SMILES Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4
InChI 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) Y Key:FEBOTPHFXYHVPL-UHFFFAOYSA-N Y
NY  (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, the Netherlands, and the United Kingdom. ^[6]

Pharmacology

Pharmacodynamics

Benperidol is a strong dopamine receptor antagonist (D₂ (K_i 0.027 nM) and D₄ (K_i 0.066 nM)) ^[7] with weaker serotonin receptor antagonism (5-HT_2A (K_i 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]

What benperidol though being developed relatively early in the history of antipsychotics is sharing (with just viewing the raw nanomolar-affinityvalues of each respective typical and also atypical antipsychotic) a unique and clearly potent selectivity of the human D2 receptor over all other human dopaminreceptors (also considered to have the greatest range of its selectivity of dopaminereceptors over the 5HT2A-serotoninereceptors, but topped from the neuroleptics Ami- and Sulpiride here ^{[10] [11]} ), since dopaminreceptors beside the centrally viewed abilitys for schizophrenic diseases namely human cognition, emotions, motorcontroll, also playing central roles in unconscious biological mechanisms, so the erose of focusing on D2 receptorblockade, also stemmed from its considered central functioning in the above mentioned human abilities accounting brainregions (striatal- and frontalregions for example) in respective. ^{[12] [13]} Though a clearly preferation of this substance to the D2 receptor over the other receptors in the D2 family (including D3 and D4 receptors, of about the two fold) are unique (compared for example with haloperidole, perphenazine (D2-D3, 0.7-0.3(0.13)) ^[14] and cariprazine (D2-D3, 0.49-0.085). ^[15]

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. ^[8]

Synthesis

4-(2-Keto-1-benzimidazolinyl)piperidine (1) is alkylated with 4-chloro-4'-Fluorobutyrophenone (2) to produce benperidol (3). ^{[16] [17]}

See also

• Timiperone has a similar chemical structure with a thiourea group instead of a urea group.
• Pimozide, bezitramide, oxiperomide, and neflumozide) are also made from 4-(1-benzimidazolinone)piperidine precursor
• Droperidol is similar, but has a tetrahydropyridine ring.

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. 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. 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. 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 K_i 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. https://pmc.ncbi.nlm.nih.gov/articles/PMC2821721/
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC5112764/
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC2802385/
13. https://pubmed.ncbi.nlm.nih.gov/31010452/
14. https://jpet.aspetjournals.org/article/S0022-3565(24)37395-1/abstract
15. https://www.cambridge.org/core/journals/cns-spectrums/article/mechanism-of-action-of-cariprazine/BE9B7B7A373A80A0B5BC8C47B47ACC12
16. Thieme
17. 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