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Legal status	Withdrawn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)[1]
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 Y
PubChem CID	2247
IUPHAR/BPS	2603
DrugBank	DB00637 Y
ChemSpider	2160 Y
UNII	7HU6337315
KEGG	D00234 Y
ChEBI	CHEBI:2896 Y
ChEMBL	ChEMBL296419 Y
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) Y Key:GXDALQBWZGODGZ-UHFFFAOYSA-N Y
(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 It was withdrawn from the market globally in 1999 because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel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]

Pharmacology

Astemizole is a histamine H1-receptor antagonist. It has anticholinergic and antipruritic effects.

Astemizole is rapidly absorbed from the gastrointestinal tract and competitively binds to histamine H₁ receptor sites in the gastrointestinal tract, uterus, blood vessels, and bronchial muscle. This suppresses the formation of edema and pruritus (caused by histamine).

Despite some earlier reports that astemizole does not cross the blood–brain barrier, several studies^[4][5] have shown high permeability and high binding to protein folds associated with Alzheimer's.

Astemizole may also act on histamine H₃ receptors, thereby producing adverse effects.^{[citation needed]}

Astemizole does also act as FIASMA (functional inhibitor of acid sphingomyelinase).^[6]

Astemizole has been researched as a treatment for Creutzfeldt-Jakob Disease (CJD).^[7]

Toxicity

Astemizole has an oral LD₅₀ of approximately 2052 mg/kg (in mice).