Benperidol Explained

Verifiedfields:	changed
Verifiedrevid:	459533587
Iupac Name:	1--1,3-dihydro-2H-benzimidazol-2-one
Width:	240
Alt2:	Ball-and-stick model of the benperidol molecule
Width2:	250
Tradename:	Anquil, Frenactil
Legal Au:	S4 (Prescription only)
Legal Us:	Rx-only
Routes Of Administration:	Oral
Elimination Half-Life:	8 hours
Cas Number:	2062-84-2
Atc Prefix:	N05
Atc Suffix:	AD07
Pubchem:	16363
Drugbank:	DB12867
Chemspiderid:	15521
Unii:	97O6X78C53
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:	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:	FEBOTPHFXYHVPL-UHFFFAOYSA-N

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

Pharmacodynamics

Benperidol is a strong dopamine receptor antagonist (D₂ (K_i 0.027 nM) and D₄ (K_i 0.066 nM)) with weaker serotonin receptor antagonism (5-HT_2A (K_i 3.75 nM)). In high doses, it has antihistaminergic and alpha-adrenergic properties. It possesses minimal anticholinergic properties.^[7]

Benperidol^[8] ! Site !! K_i (nM) !! Action !! Ref

	3.75	Antagonist	^[9]
	4,100	Antagonist
	0.027	Antagonist
	0.06	Antagonist

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.

Synthesis

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

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.

Notes and References

1. Council A, Kuenssberg V . 1974-02-01 . Benperidol - a drug for sexual offenders? . Drug and Therapeutics Bulletin . BMJ Publishing Group Ltd . 12 . 3 . 12 . 10.1136/dtb.12.3.12 . 4457302 . 44581451.
2. British National Formulary (49th), British Medical Association 2005 p 183
3. Bobon J, Collard J, Lecoq R . [Benperidol and promazine: a "double blind" comparative study in mental geriatrics] . fr . Acta Neurologica et Psychiatrica Belgica . 63 . 839–43 . October 1963 . 14092279 .
4. Book: Möller HJ, Müller WE, Bandelow . Neuroleptika: pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen; mit 136 Tabellen. . Wiss. Verlag-Ges. . 2001 . de . 3-8047-1773-X .
5. Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ . Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers . The Journal of Endocrinology . 67 . 2 . 179–88 . November 1975 . 1107462 . 10.1677/joe.0.0670179 .
6. Web site: NCATS Inxight Drugs — BENPERIDOL . 13 March 2022 .
7. Leucht S, Hartung B . Benperidol for schizophrenia . The Cochrane Database of Systematic Reviews . 2005 . 2 . CD003083 . April 2005 . 15846648 . 7017029 . 10.1002/14651858.CD003083.pub2 .
8. Web site: PDSP K_i Database . Psychoactive Drug Screening Program (PDSP). Bryan Roth . Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 11 March 2022 .
9. Li P, Snyder GL, Vanover KE . Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future . Current Topics in Medicinal Chemistry . 16 . 29 . 3385–3403 . December 2016 . 27291902 . 5112764 . 10.2174/1568026616666160608084834 .
10. https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-02-0036 Thieme
11. BE . 626307. (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to GB . 989755 . 1965-04-22 . 1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds . N.V. Research Laboratorium Dr. C. Janssen.