Article: Astemizole

Astemizole
Systematic (IUPAC) name
1-[(4-fluorophenyl)methyl]- N-[1-[2-(4-methoxyphenyl)ethyl]- 4-piperidyl]benzoimidazol-2-amine
Identifiers
CAS number	68844-77-9
ATC code	R06AX11
PubChem	2247
DrugBank	APRD00585
Chemical data
Formula	C28H31FN4O
Mol. weight	458.571
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half life	24 hours
Excretion	Fecal
Therapeutic considerations
Pregnancy cat.	C (USA)
Legal status	Unscheduled
Routes	Oral

Astemizole (marketed under the brand name Hismanal) is a second generation antihistamine drug which has a long duration of action. It has been withdrawn from the market in most countries because of rare but potentially fatal interactions with CYP34A enzyme inhibitors.

Pharmacology

Astemizole is an histamine H1-receptor antagonist. It is structurally similar to terfenadine and haloperidol (a butyrophenone antipsychotic). It has anticholinergic and antipruritic effects.

Astemizole 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).

Astemizole does not cross the blood-brain barrier, and H1 receptor binding is mostly in the peripeheral rather than central nervous system (CNS depression is thus minimal). Astemizole may also act on histamine H3 receptors, thereby producing adverse effects.

Astemizole is rapidly absorbed from the gastrointestinal tract; protein binding is around 96%.

Toxicity

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

Research

It has been reported that this drug might prevent 97% of the muscle wasting (atrophy) that occurs in immobile, bedridden patients.^[1] Testing upon mice showed that it blocked the activity of a protein present in the muscle that is involved in muscle atrophy.^[2] Recent studies have also suggested anti-malarial properties of astemizole. However the concerns for the drug's longterm effects on the heart preclude its routine use in humans for this indication.