Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loratadine is a new non-sedating antihistamine. The present studies compared loratadine and terfenadine, another non-sedating antihistamine, for their ability to inhibit the bronchial response to histamine and other autacoids which have been implicated as contributing to the symptoms of an allergic reaction. In addition, the two antihistamines were evaluated in models of immunologically mediated allergic reactions. Loratadine is a more potent inhibitor of histamine-induced bronchospasm in guinea pigs than is terfenadine. Both antihistamines exhibit marked antiserotonin activity at doses 10 times their antihistamine ED50 values. In contrast, loratadine and terfenadine produce little or no inhibition of the bronchial responses to methacholine, leukotriene C4 or platelet-activating factor. An allergic bronchospasm in guinea pigs is inhibited by loratadine (ED50 = 0.40 mg/kg, p.o.) and terfenadine (ED50 = 1.7 mg/kg, p.o.). The bronchospasm associated with allergic anaphylaxis in rats is significantly inhibited by 10 mg/kg, p.o. loratadine and 30 mg/kg, p.o. terfenadine. Loratadine exhibits antiallergy activity in vitro. At micromolar concentrations, loratadine inhibits the release of histamine from Con A and A23187-stimulated rat peritoneal mast cells and the release of histamine and leukotriene C4 from a Con A-stimulated cloned murine mast cell line.
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PMID:Antiallergic activity of loratadine, a non-sedating antihistamine. 243 4

We studied the pharmacological actions of combined histamine H1/H3 receptor blockade on the increase in nasal airway resistance (NAR) and decrease in nasal cavity volume produced by nasal exposure to compound 48/80, a mast cell degranulator. In the anesthetized cat compound 48/80 (1%) produced a maximum increase in NAR of 9.1 +/- 0.7 cmH20.L/minute. The increase in NAR in animals pretreated with a combination of the H1 antagonist, chlorpheniramine (CTM; 0.8 mg/kg i.v.) and increasing doses of the H3 antagonist, thioperamide (THIO; 1.0, 3.0, and 10.0 mg/kg i.v.) were 6.1 +/- 2.1, 4.2 +/- 1.0 and 2.2 +/- 0.7 cmH20.L/minute, respectively. A second H3 antagonist, clobenpropit (CLOB; 0.03, 0.3, and 1.0 mg/kg i.v.) combined with CTM (0.8 mg/kg i.v.) also inhibited the nasal effects of compound 48/80. When the nonsedating H1 antihistamine, loratadine (3.0 mg/kg i.v.), was substituted for CTM, it also reduced nasal congestion when given in combination with THIO (10 mg/kg i.v.). In contrast, treatment with CTM (1.0 mg/kg i.v.) and the H2 antagonist, ranitidine (RAN; 1.0 mg/kg i.v.) were without activity. Loratadine, CTM, CLOB, RAN, or THIO administered alone were inactive. The alpha-adrenergic agonist, phenylpropanolamine (PPA; 1.0 mg/kg i.v.) demonstrated decongestant effects, but in contrast to H1/H3 blockade, PPA produced a significant hypertensive effect. Using acoustic rhinometry (AcR) we found that combined i.v. CTM (1.0 mg/kg) and THIO (10 mg/kg) and combined oral CTM (10 mg/kg) and THIO (30 mg/kg) blocked the decrease in nasal cavity volume produced by intranasal compound 48/80 (1%, 50 microL). We conclude that combined H1/H3 histamine receptor blockade enhances the efficacy of an H1 antagonist by conferring decongestant activity to the H1 antihistamine. We propose that the decongestant activity of combined H1/H3 blockade may provide a novel approach for the treatment of allergic nasal congestion without the hypertensive liability of current therapies.
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PMID:Combined histamine H1 and H3 receptor blockade produces nasal decongestion in an experimental model of nasal congestion. 1058 18

Allergic rhinitis is the most common allergic disease. Pharmacological interventions are often not used in pregnancy because of alarming information in drug labels and patient information, even when evidence for safety exists.Low-risk therapies could include immunotherapy, intranasal sodium cromoglycate (cromolyn sodium), beclometasone, budesonide and first-generation antihistamines. In a meta-analysis examining the safety of first-generation antihistamines in pregnancy, 200 000 first trimester exposures failed to show increased teratogenic risk. Loratadine is the most studied second-generation antihistamine (with a total patient cohort of 2147 women who were exposed) and does not appear to increase the risk of major congenital malformations; however, it has not been as well studied as the earlier antihistamines. Since desloratadine is the principal metabolite of loratadine, it can be assumed that a similar safety profile would fit for desloratadine as was described for loratadine although no direct human studies have been done. Decongestants have not been conclusively proven to affect the fetal outcome and may be used for short-term relief when no other safer alternatives are available. Intranasal corticosteroids have not been associated with an increase in congenital malformations in humans. Based on efficacy and the fact that there would be little systemic absorption, they can be considered a first-line treatment over oral antihistamines, decongestants and mast cell stabilisers; however, the number of controlled trials in pregnancy is limited. Intranasal corticosteroids are associated with minimal systemic effects in adults and are the most effective therapy for allergic rhinitis. Benefit-risk considerations must, therefore, be done but favour their first-line use during pregnancy. Because fetal safety is paramount, recommendations should be based both on the safety of the drugs during pregnancy and the comparative efficacy of the agent in the treatment of the underlying condition. This review exemplifies the fact that there are many safe treatment options for the clinician when dealing with allergic rhinitis during pregnancy.
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PMID:Fetal safety of drugs used in the treatment of allergic rhinitis: a critical review. 1604 56