(marketed under the brand name Hismanal
) is a second generation antihistamine
drug which has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica
in 1977. It has been withdrawn from the market in most countries because of rare but potentially fatal interactions with CYP3A4
enzyme inhibitors (e.g. erythromycin
, grapefruit juice
Astemizole is an histamine H1-receptor antagonist. It is structurally similar to terfenadine
(a butyrophenone antipsychotic
). It has anticholinergic
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 peripheral 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%.
Astemizole has an oral LD50
of approximately 2052mg/kg (in mice).
It has been reported that this drug might prevent 97% of the muscle wasting (atrophy
) that occurs in immobile, bedridden patients.
Testing upon mice showed that it blocked the activity of a protein present in the muscle that is involved in muscle atrophy. 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.
Astemizole has recently been found to be a potent treatment for malaria. It has a mechanism of action similar to chloroquine but has activity even in chloroquine-resistant parasites.