Antihistamine drug

The sedation side effect commonly observed on administration of classical antihistaminic drugs has been attributed in part to the ease with which many of these compounds cross the blood brain barrier. There have been developed recently a series of agoits, for example, terfenadine (198), which cause reduced sedation by virtue of decreased penetration into the CNS. This is achieved by making them more hydrophilic. Synthesis of a related compound, ebastine (197),... 

The latter approach is used in the enantioselective determination of a Phase I metabolite of the antihistaminic drug, terfenadine. Terfenadine is metabolized to several Phase I compounds (Fig. 7-13), among which the carboxylic acid MDL 16.455 is an active metabolite for which plasma concentrations must often be determined. Although terfenadine can be separated directly on Chiralpak AD - an amy-lose-based CSP - the adsorption of the metabolite MDL 16.455 is too high to permit adequate resolution. By derivatizing the plasma sample with diazomethane, the carboxylic acid is converted selectively to the methyl ester, which can be separated in the presence of all other plasma compounds on the above-mentioned CSP Chiralpak AD [24] (Fig. 7-14). Recently, MDL 16.455 has been introduced as a new antihistaminic drug, fexofenadine. 

It was noted, however, that a subset of responses known to be triggered by histamine failed to be blocked by the classical antihistaminic drugs. This, as well as further sophisticated pharmacological work, led to the classification of histamine receptors as and Hg. To simplify grossly, the receptor controls the responses familiar to every hayfever sufferer these effects can be alleviated readily by classicial antihistamines. The latter interestingly bear little or no structural similarity to histamine... 

Hydroxy or hydroxymethyl groups attached to quinolizine substrates normally show the expected reactivity. For instance, compound 109 was linked to histamine receptor antagonists by esterification with succinic anhydride followed by amidification with the antihistaminic drug to give the fluorescently labeled stmcture 110 for in vivo studies of receptor binding (Scheme 13) <2003BML1717>. 

Since the order of increasing CL intensity for alkyl amines reacted with Ru(bpy)32+ is tertiary amines > secondary amines > primary amines, pharmaceutical compounds bearing a tertiary amine function (e.g., antihistamine drugs [99], anticholinergic drugs [100], erythromycin [101], and its derivatives [102]) have been sensitively determined after HPLC separation (Table 3). The method was applied to the detection of d- and L-tryptophan (Trp) after separation by a ligand-exchange HPLC [103], The detection limits for d- and L-Trp were both 0.2 pmol per injection. Oxalate in urine and blood plasma samples has also been determined by a reversed-phase ion-pair HPLC (Fig. 18) [104], Direct addition of... 

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

Interactions with the hERG cardiac channel leading to QT interval prolongation (e.g., some antipsychotics and antihistamines drugs)... 

Matsumoto S, Hirama T, Matsubara T, Nagata K, Yamazoe Y. 2002. Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole. Drug Metab... 

Cetirizine is a non-sedating antihistamine drug that may be used for symptomatic relief in allergic rhinitis (hay fever) as it reduces rhinorrhoea and sneezing. Fexofenadine is an active metabolite of terfenadine (another antihistamine). 

Q82 A patient with prostatic hypertrophy who has a chesty cough could be advised to use carbocisteine syrup. Carbocisteine syrup does not contain antihistamine drugs. 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

Figure 6. Heat map of a small cluster of related antihistaminic drugs. 149 pharmacological assays are clustered on the X-axis and 10 compounds are clustered on the Y-axis. Clustering is performed using Pearson correlation and complete linkage using a pICso data set. For nonhits with primary screening % inhibition values of less than 20%, a default pICso value of 3.5 was used. Non-hits and above 20% inhibition received a default pICso value of 4.0. The pICso values range from the default value of 3.5 (blue-green) to 9 (red). Black spaces indicate data that is missing due to compound interference with the detection method.

The most common Hj antihistamine drugs are structurally similar to histamine with a substituted ethylamine side chain however, they have two aromatic rings and can be formally represented by the general formula ... 

Diphenylpyraline is an antihistamine drug with anticholinergic and sedative action. 

Traditional or Hj antihistamine drugs block many effects caused by histamine however, it turns out that they are not able to withstand events mediated by H2 receptors, in particular excess gastric juice secretion. In 1977 an H2-receptor antagonist, cimetidine, was proposed, which revolutionized stomach ulcer treatment. Later on, ranitidine was proposed, followed by drugs with minor structural and pharmacological differences such as famotidine and nizatidine. 

Cimetidine is a representative of first-generation antihistamine drugs that block H2 receptors. The main pharmacological effect of cimetidine is the suppression of gastric juice secretion associated with H2 receptors of the stomach walls. It suppresses both basal and stimulated hyckochloric acid produced by food as well as histamine and gastrine, which simultaneously lower pepsin activity. 

Walsh GM et al. New insights into the second-generation antihistamines. Drugs 2001 61 207-236. 

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