10-Hydroxyketotifen

10-Hydroxyketotifen (WR621365)^[1] is a biologically inactive metabolite of ketotifen. ^[3][4][5] Despite the mainstream scientific consensus that 10-hydroxyketotifen is a biologically inactive compound, its pharmacological properties are not very well studied outside the context of ketotifen, therefore, 10-hydroxyketotifen may still possess biological activity similarly to norketotifen, another metabolite of ketotifen.^[1]

10-Hydroxyketotifen

Names
IUPAC name 4-(1-methylpiperidin-4-ylidene)-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-ol
Other names 10-hydroxy-ketotifen, WR621365,[1] NSC282481[2]
Identifiers
CAS Number	43076-12-6
3D model (JSmol)	Interactive image
ChemSpider	286324
PubChem CID	323312
CompTox Dashboard (EPA)	DTXSID20314398
InChI InChI=1S/C19H21NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11,17,21H,6-7,9-10,12H2,1H3 Key: TZHJFZBFWVCFAA-UHFFFAOYSA-N
SMILES OC1c2c(/C(c3ccccc3C1)=C4CCN(CC\4)C)ccs2
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Metabolic role

Main article: Ketotifen

Ketotifen is an antihistamine medication which metabolizes to several compounds, including 10-hydroxyketotifen. Ketotifen, like other antihistamines,^[6][7] is mainly metabolized by the cytochrome P450 (CYP) enzymes, especially CYP3A4^[8][9] in the liver. The CYP enzymes are responsible for the oxidation and demethylation of ketotifen, producing the major metabolites norketotifen and 10-hydroxyketotifen. Norketotifen is pharmacologically active and has a similar potency as ketotifen, while 10-hydroxyketotifen is inactive. The metabolites are then conjugated with glucuronic acid or sulfate and excreted in the urine and feces.^[10][11]

The definition and measurement of biological activity of drugs can be complex: biological activity is often defined in terms of the ability of a molecule to effect a change in a biological process, which can be quantified and measured in various ways; as such, even if 10-hydroxyketotifen is currently deemed inactive, it is possible that under certain conditions or within specific biological assays, some level of activity might be observed.^[1][12]