Ketanserin

Ketanserin
Clinical data
Trade namesSufrexal, Serefrex
Other namesR-41468; R41468; R-41,468; KJK-945; R-49945; R49945
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability50%[1][2]
Protein binding95% (mainly albumin[2][3]
MetabolismExtensive[3]
Metabolites• Ketanserin-ol[3]
Elimination half-life10–29 hours[4][1][2]
ExcretionUrine; 2% unchanged[3]
Identifiers
IUPAC name
  • 3-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}quinazoline-2,4(1H,3H)-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.070.598
Chemical and physical data
FormulaC22H22FN3O3
Molar mass395.434 g·mol−1
3D model (JSmol)
SMILES
  • c1ccc2c(c1)c(=O)n(c(=O)[nH]2)CCN3CCC(CC3)C(=O)c4ccc(cc4)F
InChI
  • InChI=1S/C22H22FN3O3/c23-17-7-5-15(6-8-17)20(27)16-9-11-25(12-10-16)13-14-26-21(28)18-3-1-2-4-19(18)24-22(26)29/h1-8,16H,9-14H2,(H,24,29) Y
  • Key:FPCCSQOGAWCVBH-UHFFFAOYSA-N Y
  (verify)

Ketanserin, sold under the brand name Sufrexal, is an antihypertensive agent which is used to treat arterial hypertension and vasospastic disorders.[5][6][3] It is also used in scientific research as an antiserotonergic agent in the study of the serotonin system; specifically, the 5-HT2 receptor family.[7] The drug is taken by mouth.[6][3]

Side effects of ketanserin include dizziness, tiredness, edema, dry mouth, weight gain, and QT interval prolongation.[6] Ketanserin acts as a selective antagonist of the serotonin 5-HT2A, α1-adrenergic, and histamine H1 receptors.[6][8][9] It also shows lower affinity for various other targets.[9]

Ketanserin was discovered at Janssen Pharmaceutica in 1980.[10][11] It was the first serotonin 5-HT2A receptor antagonist to be discovered that showed selectivity over other serotonin receptors.[9] The drug is not available in the United States[1] and is mostly no longer marketed throughout the rest of the world.[12][13]

  1. ^ a b c Wolverton SE (8 March 2007). Comprehensive Dermatologic Drug Therapy (2 ed.). Elsevier Health Sciences. ISBN 978-1-4377-2070-9.
  2. ^ a b c Hideya Saitō, Masaru Minami, eds. (1992). Antihypertensive Drugs Today. VSP. pp. 191–. ISBN 978-90-6764-140-1. OCLC 231351327.
  3. ^ a b c d e f Persson B, Heykants J, Hedner T (April 1991). "Clinical pharmacokinetics of ketanserin". Clin Pharmacokinet. 20 (4): 263–279. doi:10.2165/00003088-199120040-00002. PMID 2036747.
  4. ^ Cold GE, Dahl BL (11 November 2013). Topics in Neuroanaesthesia and Neurointensive Care: Experimental and Clinical Studies upon Cerebral Circulation, Metabolism and Intracranial Pressure. Springer Science & Business Media. pp. 193–. ISBN 978-3-662-04845-0. OCLC 1076237896.
  5. ^ Symoens J (June 1990). "Ketanserin: a novel cardiovascular drug". Blood Coagul Fibrinolysis. 1 (2): 219–224. PMID 2130934.
  6. ^ a b c d Brogden RN, Sorkin EM (December 1990). "Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease". Drugs. 40 (6): 903–949. doi:10.2165/00003495-199040060-00010. PMID 2079001.
  7. ^ O'Donnell J, Ahuja GD (2005). Drug Injury: Liability, Analysis, and Prevention. Lawyers & Judges Publishing Company. pp. 304–. ISBN 978-0-913875-27-8.
  8. ^ Awouters F (1985). "The pharmacology of ketanserin, the first selective serotonin S2‐antagonist". Drug Development Research. 6 (4). Wiley: 263–300. doi:10.1002/ddr.430060402. ISSN 0272-4391.
  9. ^ a b c Casey AB, Cui M, Booth RG, Canal CE (June 2022). ""Selective" serotonin 5-HT2A receptor antagonists". Biochem Pharmacol. 200: 115028. doi:10.1016/j.bcp.2022.115028. PMC 9252399. PMID 35381208. Since its discovery by Janssen Pharmaceuticals in 1981 (35), the quinazoline derivative ketanserin is among the most widely used tools for probing 5-HT2AR function in preclinical research (26–28, 36), and the sole antagonist used to delineate the 5-HT2AR-dependent effects of serotonergic psychedelics in humans (37–41). Although ketanserin was the first 5-HT2AR antagonist discovered that lacks high affinity for other serotonin and dopamine receptors, it is less appreciated that it has high affinity at several aminergic receptors, including α1A-, α1B-, α1D-adrenergic, and histamine H1 receptors (35, 42–44), as well as, moderate affinity at α2B-adrenergic and 5-HT2C receptors (Table 1). These off-target activities limit the utility of ketanserin as a specific tool for assessing 5-HT2AR activity.
  10. ^ Healy D (1 July 2009). The Creation of Psychopharmacology. Harvard University Press. pp. 252–253. ISBN 978-0-674-03845-5.
  11. ^ Schwartz H (August 1989). Breakthrough: the discovery of modern medicines at Janssen. Skyline Pub. Group. p. 74. ISBN 978-1-56019-100-1.
  12. ^ Cite error: The named reference IndexNomininum2004 was invoked but never defined (see the help page).
  13. ^ "Ketanserin (International database)". Drugs.com. 6 October 2024. Retrieved 8 October 2024.
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