Ketanserin

Title: Ketanserin
CAS Registry Number: 74050-98-9
CAS Name: 3-[2-[4-(4-Fluorobenzoyl)-1-piperidinyl]ethyl]-2,4[1H,3H]-quinazolinedione
Manufacturers' Codes: R-41468
Trademarks: Ketensin (Janssen); Serefrex (Janssen); Taseron (Janssen)
Molecular Formula: C22H22FN3O3
Molecular Weight: 395.43
Percent Composition: C 66.82%, H 5.61%, F 4.80%, N 10.63%, O 12.14%
Literature References: Specific serotonin (5HT2)-receptor antagonist. Prepn: J. Vandenbeck et al., EP 13612; eidem, US 4335127 (1980, 1982 both to Janssen). X-ray structure: O. M. Peeters et al., Cryst. Struct. Commun. 11, 375 (1982). Receptor binding profile: J. E. Leysen et al., Life Sci. 28, 1015 (1981). Pharmacology: J. M. Van Neuten et al., J. Pharmacol. Exp. Ther. 218, 217 (1981). HPLC determn in plasma: A. T. Kacprowicz et al., J. Chromatogr. 272, 417 (1983). Clinical efficacy in intermittent claudication: J. De Cree et al., Lancet 2, 775 (1984); in Raynaud's phenomenon: J. R. Seibold, A. H. M. Jageneau, Arthritis Rheum. 27, 139 (1984); in hypertension: A. Amery et al., J. Cardiovasc. Pharmacol. 6, 182 (1984). Series of articles on pharmacology and clinical studies: ibid. 7, Suppl. 7, S1-S182 (1985); on pharmacokinetics and metabolism: Arzneim.-Forsch. 38, 775-800 (1988). Review of pharmacology and clinical efficacy in hypertension and vascular disease: R. N. Brogden, E. M. Sorkin, Drugs 40, 903-949 (1990).
Properties: Crystals from 4-methyl-2-pentanone, mp 227-235°. Soly (g/100 ml): 0.001 in water; 0.038 in ethanol; 2.34 in DMF. pKa 7.5.
Melting point: mp 227-235°
pKa: pKa 7.5
Derivative Type: Tartrate
CAS Registry Number: 83846-83-7
Manufacturers' Codes: R-49945
Trademarks: Ket (Irbi); Perketan (Inverni); Serepress (Formenti); Sufrexal (Janssen)
Molecular Formula: C22H22FN3O3.C4H6O6
Molecular Weight: 545.51
Percent Composition: C 57.25%, H 5.17%, F 3.48%, N 7.70%, O 26.40%
Therap-Cat: Antihypertensive.
Keywords: Antihypertensive; Serotonin Receptor Antagonist.
Ketazolam Kethoxal Ketipic Acid Ketorolac Khat

Ketanserin
Ketanserin.png
Systematic (IUPAC) name
3-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}quinazoline-2,4(1H,3H)-dione
Clinical data
AHFS/Drugs.com International Drug Names
Legal status  ?
Identifiers
CAS number 74050-98-9 YesY
ATC code C02KD01 QD03AX90
PubChem CID 3822
IUPHAR ligand 88
ChemSpider 3690 YesY
UNII 97F9DE4CT4 YesY
KEGG D02363 YesY
ChEBI CHEBI:6123 N
ChEMBL CHEMBL51 YesY
Chemical data
Formula C22H22FN3O3 
Mol. mass 395.43 g/mol
 N (what is this?)  (verify)

Ketanserin (R41468) is a drug with affinity for multiple G protein-coupled receptors (GPCR). It is a highly selective antagonist for serotonin 5-HT2A receptors, but also has moderate selectivity for 5-HT2C receptors and for alpha-1 adrenergic receptors, and very high affinity for histamine H1 receptors. Therefore, ketanserin can not be used to reliably discriminate between the effects of 5-HT2A and 5-HT2C receptors when both are present in an experimental system. Furthermore, when alpha-1 and H1 receptors are present, the effects of ketanserin can potentially represent a complex interaction of serotonin, adrenergic, and histamine receptor systems. Complicating the matter further is the fact that ketanserin has moderate affinity for delta-1t adrenergic receptor (~200 nM) and 5-HT6 (~300 nM) receptors as well as weak affinity for dopamine D1 and D2 receptors (~300 nM and ~500 nM respectively). Ketanserin at levels of 500 nM or greater are thus potentially affecting at least 8 different GPCRs from 4 different families. (All affinity levels taken from the NIMH Psychoactive Drug Screening Program database [1])

Receptors for which ketanserin has high affinity binding:

  • 5-HT2A = 2-3 nM (rat and human)
  • 5-HT2C = 50 nM (rat), 100 nM (human)
  • alpha-1 adrenergic = ~40 nM
  • Histamine H1 = 2 nM

Solubility:

  • 6 mg/mL 0.1 M HCl
  • 10 mM H20
  • 3.3 mg/mL ethanol
  • 52 mg/mL DMSO

Ketanserin was discovered at Janssen Pharmaceutica in 1980.