Astemizole (R43512, marketed under the brand name Hismanal) was a second-generation antihistamine drug that 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 It has been withdrawn from the market in most countries because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade).
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).
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.
It has been reported that this drug might prevent much of the muscle wasting (atrophy) that occurs in immobile, bedridden patients. An experiment on a small number of mice showed that astemizole blocked the activity of a protein present in muscle that is involved in muscle atrophy. However, the concerns for the drug's long-term 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.
^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". J. Cardiovasc. Electrophysiol.10 (6): 836–43. PMID10376921.
^Di, Li; Kerns, Edward H; Fan, Kristi; McConnell, Oliver J; Carter, Guy T (7 March 2003). "High throughput artificial membrane permeability assay for blood–brain barrier". European Journal of Medicinal Chemistry38 (3): 223–232. doi:10.1016/S0223-5234(03)00012-6.
^Wang X, Hockerman GH, Green Iii HW, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL (May 24, 2006). "Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway". FASEB J20 (9): 1531–3. doi:10.1096/fj.05-5350fje. PMID16723379.
^Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ (2006). "A clinical drug library screen identifies astemizole as an antimalarial agent". Nat Chem Biol2 (8): 415–16. doi:10.1038/nchembio806. PMID16816845.