Astemizole 2966927 221299284 2008-06-23T22:33:45Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{Drugbox| |IUPAC_name = ''1-[(4-fluorophenyl)methyl]- N-[1-[2-(4-methoxyphenyl)ethyl]- 4-piperidyl]benzoimidazol-2-amine'' | image = Astemizole.svg | width=200 | CAS_number=68844-77-9 | ATC_prefix=R06 | ATC_suffix=AX11 | ATC_supplemental= | PubChem=2247 | DrugBank=APRD00585 | C=28 | H=31 | F=1 | N=4 | O=1 | molecular_weight = 458.571 | bioavailability= ? | metabolism = [[Hepatic]] | elimination_half-life= 24 hours | excretion = [[Fecal]] | pregnancy_category = C ([[United States|USA]]) | legal_status = Unscheduled | routes_of_administration= Oral }} '''Astemizole''' (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 It has been withdrawn from the market in most countries because of rare but potentially fatal interactions with [[CYP3A4]] enzyme inhibitors (e.g. [[erythromycin]], [[grapefruit]]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). ==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 [[peripheral nervous system|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%. ==Toxicity== Astemizole has an oral LD<sub>50</sub> 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.<!-- --><ref "ND2006">{{cite news | url=http://www2.netdoctor.co.uk/news/index.asp?y=2006&m=5&d=25&id=123026 |title = Drug 'could stop muscle wasting' |publisher = NetDoctor.co.uk |date = 2006-05-25 |accessdate = 2006-05-27}}</ref> Testing upon mice showed that it blocked the activity of a protein present in the muscle that is involved in muscle atrophy.<!-- --><ref name="FASEBJ2006-Wang">{{cite journal | author=Wang X, Hockerman GH, Green Iii HW, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL | title=Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway | journal=FASEB J | year=2006 | month=May24 | pmid=16723379 | doi=10.1096/fj.05-5350fje | volume=20 | pages=1531}}</ref> Recent studies have also suggested [[malaria|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.<ref>{{cite journal | title=A clinical drug library screen identifies astemizole as an antimalarial agent | author=Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ | journal=Nat Chem Biol | year=2006 | volume=2 | pages=415&ndash;16 | doi=10.1038/nchembio806 | pmid=16816845 }}</ref> ==External links== * [http://www.rxlist.com/cgi/generic/astem.htm RxList.com - Astemizole] * [http://www.hc-sc.gc.ca/dhp-mps/medeff/advers-react-neg/fs-if/astemizole_e.html Statement on Astemizole from Health Canada] ==Footnotes== <references/> {{antihistamines}} [[Category:Antihistamines]] [[Category:Withdrawn drugs]] [[de:Astemizol]] [[es:Astemizol]] [[pl:Astemizol]] [[th:แอสเทมมีโซล]]