Astemizole

Astemizole
Clinical data
AHFS/Drugs.com	Multum Consumer Information
MedlinePlus	a600034
Pregnancy; category	C (USA);
Routes of; administration	Oral
ATC code	R06AX11 (WHO) ;
Legal status
Legal status	Withdrawn;
Pharmacokinetic data
Protein binding	~96%
Metabolism	Hepatic (CYP3A4)
Elimination half-life	24 hours
Excretion	Fecal
Identifiers
	IUPAC name 1-[(4-fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidyl]benzoimidazol-2-amine;
CAS Number	68844-77-9 ;
PubChem CID	2247;
IUPHAR/BPS	2603;
DrugBank	DB00637 ;
ChemSpider	2160 ;
UNII	7HU6337315;
KEGG	D00234 ;
ChEBI	CHEBI:2896 ;
ChEMBL	ChEMBL296419 ;
CompTox Dashboard (EPA)	DTXSID9020110 ;
ECHA InfoCard	100.065.837
Chemical and physical data
Formula	C28H31FN4O
Molar mass	458.581 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Fc1ccc(cc1)Cn2c5ccccc5nc2NC4CCN(CCc3ccc(OC)cc3)CC4;
	InChI InChI=1S/C28H31FN4O/c1-34-25-12-8-21(9-13-25)14-17-32-18-15-24(16-19-32)30-28-31-26-4-2-3-5-27(26)33(28)20-22-6-10-23(29)11-7-22/h2-13,24H,14-20H2,1H3,(H,30,31) ; Key:GXDALQBWZGODGZ-UHFFFAOYSA-N ;
	(verify)

Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It was withdrawn from the market globally in 1999 because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade).^[2]^[3]

^ Matsumoto S, Yamazoe Y (February 2001). "Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine". British Journal of Clinical Pharmacology. 51 (2): 133–142. doi:10.1111/j.1365-2125.2001.01292.x. PMC 2014443. PMID 11259984.
^ Zhou Z, Vorperian VR, Gong Q, Zhang S, January CT (June 1999). "Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole". Journal of Cardiovascular Electrophysiology. 10 (6): 836–843. doi:10.1111/j.1540-8167.1999.tb00264.x. PMID 10376921. S2CID 25655101.
^ Charles O, Onakpoya I, Benipal S, Woods H, Bali A, Aronson JK, et al. (2019). "Withdrawn medicines included in the essential medicines lists of 136 countries". PLOS ONE. 14 (12): e0225429. Bibcode:2019PLoSO..1425429C. doi:10.1371/journal.pone.0225429. PMC 6887519. PMID 31791048.

[pmid11259984-1] Matsumoto S, Yamazoe Y (February 2001). "Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine". British Journal of Clinical Pharmacology. 51 (2): 133–142. doi:10.1111/j.1365-2125.2001.01292.x. PMC 2014443. PMID 11259984.

[pmid10376921-2] Zhou Z, Vorperian VR, Gong Q, Zhang S, January CT (June 1999). "Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole". Journal of Cardiovascular Electrophysiology. 10 (6): 836–843. doi:10.1111/j.1540-8167.1999.tb00264.x. PMID 10376921. S2CID 25655101.

[3] Charles O, Onakpoya I, Benipal S, Woods H, Bali A, Aronson JK, et al. (2019). "Withdrawn medicines included in the essential medicines lists of 136 countries". PLOS ONE. 14 (12): e0225429. Bibcode:2019PLoSO..1425429C. doi:10.1371/journal.pone.0225429. PMC 6887519. PMID 31791048.

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