Astemizole

Chemical Name 1-[(4-Fluorophenyl)methyl] -N-[1 -[2-(4-methoxyphenyl)ethyl] -4-piperi-dinyl] -1 H-benzimidazol-2-amine 

This second-generation histamine HI receptor blocker was put on the world market in the 1980s for the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria [14], Janssen Pharmaceuticals marketed this dmg under the brand name Hismanal. The major benefit of these antihistamines was their 

Molecular formula C2aH3,FN40 Molecular weight 458.6 CAS Registry No. 68844-77-9 

Sample preparation 2 mL Whole blood or plasma + 2 mL buffer + 5 mL chloroform isopropeinolrn-heptane 60 14 26, shake gently horizontally for 10 min, centrifuge at 2800 g for 10 min. Remove the lower organic layer and evaporate it to dryness under vacuum at 45°, reconstitute the residue in 100 p,L mobile phase, centrifuge at 2800 g for 5 min, inject a 50 pL aliquot of the supernatant. (Buffer was saturated ammonium chloride solution 25% diluted with water, adjusted to pH 9.5 with 25% ammonia solution.) 

Mobile phase MeOH THF buffer 65 5 30 (Buffer was 0.68 g/L (10 mM (sic)) KH2PO4 adjusted to pH 2.6 with concentrated orthophosphoric acid.) (At the end of each session wash the column with water for 1 h and MeOH for 1 h, re-equilibrate for 30 min.) 

Interfering bisoprolol, cetirizine, chlorpheniramine, cibenzoUne, diltiazem, glibomuride, loprazolam, medifoxamine, moperone, nicardipine, vinblastine 

Tracqui, A. Kintz, P. Meingin, P. Systematic toxicological analysis using HPLC/DAD. J.Forensic Sci., 1995, 40, 254-262 

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The sales of antagonists of receptors, eg, diphenhydramine, terfenadine, and astemizole, used in the treatment of allergic diseases, represent 1% of the overall pharmaceutical market, ie, 1.7 biUion (U.S.). antagonists, eg, cimetidine and ranitidine, are effective in peptic ulcer disease and esophageal reflux. Sales represent 3.5% of the world market, ie, 6 biUion (U.S.). agonists or antagonists have not yet found a clear indication. 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

Congenital Long QT syndrome Human-ether-a-go-go-related protein (HERG) E-4031, astemizole, cisapride... 

C7H4N2O2S 2719-30-4) see Astemizole isovaleraldehyde (C5H10O 590-86-3) sec Bulizide isovaleric acid... 

In some patients, torsades de pointes maybe of short duration and may terminate spontaneously. However, torsades de pointes may not terminate on its own, and if left untreated, may degenerate into VF and result in sudden cardiac death.13 Several drugs, including terfenadine, astemizole, and cisapride have been withdrawn from the United States market as a result of causing deaths due to torsades de pointes. 

Antihistamine astemizole, terfenadine Estrogen ethinyl estradiol GI cisapride... 

Azole anti fungal s Arrhythmias with astemizole... 

Fig. 10.10. DQF-COSY data of astemizole (5). The black bars indicate the contiguous spin system drawn with arrows on the relevant portion of astemizole.

Fig. 10.11. 2D NOESY data of astemizole (5). The mixed phase correlations in the aromatic region (boxed) are examples of the artifacts described in the text.

Astemizole Hismanal Antihistamine Drug-drug interaction 1988 U.S. 1999 11... 

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