Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...

drug that has a long duration of action. Astemizole was discovered by

Janssen Pharmaceutica Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...

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 It was withdrawn from the market globally in 1999 because of rare but potentially fatal side effects ( QTc interval prolongation and related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 Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

due to

hERG hERG (the human '' Ether-à-go-go''-Related Gene) is a gene () that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel (sometimes simply denoted as 'hERG') is best known for its contribution to th ...

channel blockade).

Pharmacology

Astemizole is a histamine H1-receptor antagonist. It has

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

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 Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

(caused by histamine). Despite some earlier reports that astemizole does not cross the blood–brain barrier, several studies 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. Astemizole does also act as

FIASMA Functional inhibitors of acid sphingomyelinase, or FIASMA, is a large group of pharmacological compounds inhibiting the enzyme acid sphingomyelinase (ASM, EC 3.1.4.12). This enzyme is mainly located within the lysosome, where it cleaves sphingomyeli ...

(functional inhibitor of

acid sphingomyelinase Acid sphingomyelinase is one of the enzymes that make up the sphingomyelinase (SMase) family, responsible for catalyzing the breakdown of sphingomyelin to ceramide and phosphorylcholine. They are organized into alkaline, neutral, and acidic SMase de ...

Toxicity

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

References

External links

Statement on Astemizole from Health Canada
{{Histaminergics Phenethylamines Belgian inventions Benzimidazoles Fluoroarenes H1 receptor antagonists HERG blocker Janssen Pharmaceutica Phenol ethers Piperidines Withdrawn drugs