Emedastine
(Synonyms: 依美斯汀) 目录号 : GC39378
A histamine H1 receptor antagonist
Cas No.:87233-61-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Emedastine is a histamine H1 receptor antagonist (Ki = 1.3 nM).1 It is selective for histamine H1 over H2 and H3 receptors (Kis = 49 and 12.43 ?M, respectively), as well as α1-, α2-, and β1-adrenergic and dopamine D1 and D2 receptors, and the serotonin (5-HT) receptor subtypes 5-HT1 and 5-HT2 at 10 ?M.1,2 Emedastine inhibits histamine-induced phosphoinositide turnover and intracellular calcium mobilization in primary human conjunctival epithelial cells (HCECs; IC50s = 1.6 and 2.9 nM, respectively).3 It also inhibits histamine-stimulated secretion of IL-6, IL-8, and GM-CSF by primary HCECs (IC50s = 2.23, 3.42, and 1.50 nM, respectively).4 Ocular application of emedastine prior to histamine challenge inhibits vascular permeability in guinea pigs.2 Formulations containing emedastine have been used in the treatment of allergic conjunctivitis.
1.Sharif, N.A., Su, S.X., and Yanni, J.M.Emedastine: A potent, high affinity histamine H1-receptor-selective antagonist for ocular use: Receptor binding and second messenger studiesJ. Ocul. Pharmacol.10(4)653-664(1994) 2.Yanni, J.M., Stephens, D.J., Parnell, D.W., et al.Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist for topical ocular useJ. Ocul. Pharmacol.10(4)665-675(1994) 3.Sharif, N.A., Xu, S.X., Magnino, P.E., et al.Human conjunctival epithelial cells express histamine-1 receptors coupled to phosphoinositide turnover and intracellular calcium mobilization: Role in ocular allergic and inflammatory diseasesExp. Eye Res.63(2)169-178(1996) 4.Weimer, L.K., Gamache, D.A., and Yanni, J.M.Histamine-stimulated cytokine secretion from human conjunctival epithelial cells: Inhibition by the histamine H1 antagonist emedastineInt. Arch. Allergy. Immunol.115(4)288-293(1998)
| Cas No. | 87233-61-2 | SDF | |
| 别名 | 依美斯汀 | ||
| Canonical SMILES | CN1CCN(C2=NC3=CC=CC=C3N2CCOCC)CCC1 | ||
| 分子式 | C17H26N4O | 分子量 | 302.41 |
| 溶解度 | DMSO: 125 mg/mL (413.35 mM); Ethanol: 100 mg/mL (330.68 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3068 mL | 16.5338 mL | 33.0677 mL |
| 5 mM | 0.6614 mL | 3.3068 mL | 6.6135 mL |
| 10 mM | 0.3307 mL | 1.6534 mL | 3.3068 mL |
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Emedastine difumarate: a review of its potential ameliorating effect for tissue remodeling in allergic diseases
Expert Opin Pharmacother 2009 Aug;10(11):1859-67.PMID:19558341DOI:10.1517/14656560903078410.
Background: Emedastine difumarate, a selective histamine-H1 receptor antagonist and effective antiallergic agent, inhibits various clinical symptoms of allergic rhinitis, allergic conjunctivitis, urticaria, allergic dermatitis, pruritus cutaneous, and prurigo. In addition to greater efficacy than other antihistamines, Emedastine difumarate produces no adverse cardiovascular effects and exhibits minimal anticholinergic activity. Moreover, a recent study revealed that the effect of Emedastine difumarate on inhibition of histamine-induced collagen synthesis in vitro was greater in dermal fibroblasts than in nasal mucosa fibroblasts. This result indicates that there are tissue-specific effects of Emedastine difumarate and that it may be more effective for treating fibrosis in skin than in nasal mucosa. However, the mechanism and role of tissue remodeling is less well established for allergic skin diseases and allergic conjunctivitis, in comparison to respiratory allergic diseases. Objective: This review outlines the involvement of histamine in the pathogenesis of tissue remodeling in a variety of organs, and presents the evidence for the effect of antihistamines on this process. Furthermore, this review also discusses antihistamines as an intervention strategy in tissue remodeling. Methods: The scientific literature, published abstracts, and selected textbooks were reviewed. Results/conclusion: Although additional evidence is required, emerging evidence suggests that Emedastine difumarate may be of value in the prevention of excess tissue remodeling in allergic skin inflammation.
H1-antihistamines for chronic spontaneous urticaria
Cochrane Database Syst Rev 2014 Nov 14;2014(11):CD006137.PMID:25397904DOI:10.1002/14651858.CD006137.pub2.
Background Chronic spontaneous urticaria (CSU) is characterised by the development of crops of red, itchy, raised weals or hives with no identifiable external cause.Objectives To assess the effects of H1-antihistamines for CSU.Search methods We searched the following databases up to June 2014: Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE(from 1946), EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers and checked articles for references to relevant randomised controlled trials.Selection criteria We included randomised controlled trials of H1-antihistamines for CSU. Interventions included single therapy or a combination of H1-antihistamines compared with no treatment (placebo) or another active pharmacological compound at any dose.Data collection and analysis We used standard methodological procedures as expected by The Cochrane Collaboration.Our primary outcome measures were proportion of participants with complete suppression of urticaria: 'good or excellent' response,50% or greater improvement in quality of life measures, and adverse events.We present risk ratios (RR) with 95% confidence intervals(CIs). Main results We identified 73 studies (9759 participants); 34 studies provided data for 23 comparisons. The duration of the intervention was up to two weeks (short-term) or longer than two weeks and up to three months (intermediate-term).Cetirizine 10mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this same outcome, comparison of desloratadine versus placebo in the intermediate term (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97, 95% CI 1.04 to 245.04)favoured desloratadine, but no differences were seen between 5 mg and 10 mg for short-term treatment.Levocetirizine 20 mg per day (short-term) was more effective for complete suppression of urticaria compared with placebo (RR 20.87,95% CI 1.37 to 317.60), and at 5 mg was effective in the intermediate term (RR 52.88, 95% CI 3.31 to 843.81) but not in the shortterm, nor was 10 mg effective in the short term.Rupatadine at 10 mg and 20 mg in the intermediate term achieved a 'good or excellent response' compared with placebo (RR 1.35,95% CI 1.03 to 1.77).Loratadine (10 mg) versus placebo (RR 1.86, 95% CI 0.91 to 3.79) and loratadine (10 mg) versus cetirizine (10 mg) (RR 1.05, 95%CI 0.76 to 1.43) over short-term and intermediate-term treatment showed no significant difference for 'good or excellent response' or for complete suppression of urticaria, respectively.Loratadine (10 mg) versus desloratadine (5 mg) (intermediate-term) showed no statistically significant difference for complete suppression of urticaria (RR 0.91, 95% CI 0.78 to 1.06) or for 'good or excellent response' (RR 1.04, 95% CI 0.64 to 1.71). For loratadine(10 mg) versus mizolastine (10 mg) (intermediate-term), no statistically significant difference was seen for complete suppression of urticaria (RR 0.86, 95% CI 0.64 to 1.16) or for 'good or excellent response' (RR 0.88, 95% CI 0.55 to 1.42).Loratadine (10mg) versus Emedastine (2mg) (intermediate-term) showed no statistically significant difference for complete suppression(RR 1.04, 95% CI 0.78 to 1.39) or for 'good or excellent response' (RR 1.09, 95% CI 0.96 to 1.24); the quality of the evidence was moderate for this comparison.No difference in short-term treatment was noted between loratadine (10mg) and hydroxyzine (25mg) in terms of complete suppression(RR 1.00, 95% CI 0.32 to 3.10).When desloratadine (5 to 20 mg) was compared with levocetirizine (5 to 20 mg), levocetirizine appeared to be the more effective (P value < 0.02).In a comparison of fexofenadine versus cetirizine, more participants in the cetirizine group showed complete suppression of urticaria(P value < 0.001).Adverse events leading to withdrawals were not significantly different in the following comparisons: cetirizine versus placebo at 10 mg and 20 mg (RR 3.00, 95% CI 0.68 to 13.22); desloratadine 5 mg versus placebo (RR 1.46, 95% CI 0.42 to 5.10); loratadine 10 mg versus mizolastine 10 mg (RR 0.38, 95% CI 0.04 to 3.60); loratadine 10mg versus Emedastine 2mg (RR 1.09, 95%CI 0.07 to 17.14);cetirizine 10 mg versus hydroxyzine 25 mg (RR 0.78, 95% CI 0.25 to 2.45); and hydroxyzine 25 mg versus placebo (RR 3.64, 95%CI 0.77 to 17.23), all intermediate term.No difference was seen between loratadine 10 mg versus mizolastine 10 mg in the proportion of participants with at least 50%improvement in quality of life (RR 3.21, 95% CI 0.32 to 32.33).Authors' conclusions Although the results of our review indicate that at standard doses of treatment, several antihistamines are effective when compared with placebo, all results were gathered from a few studies or, in some cases, from single-study estimates. The quality of the evidence was affected by the small number of studies in each comparison and the small sample size for many of the outcomes, prompting us to downgrade the quality of evidence for imprecision (unless stated for each comparison, the quality of the evidence was low).No single H1-antihistamine stands out as most effective. Cetirizine at 10 mg once daily in the short term and in the intermediate term was found to be effective in completely suppressing urticaria. Evidence is limited for desloratadine given at 5 mg once daily in the intermediate term and at 20 mg in the short term. Levocetirizine at 5 mg in the intermediate but not short term was effective for complete suppression. Levocetirizine 20 mg was effective in the short term, but 10 mg was not. No difference in rates of withdrawal due to adverse events was noted between active and placebo groups. Evidence for improvement in quality of life was insufficient.
Emedastine-ketoconazole: pharmacokinetic and pharmacodynamic interactions in healthy volunteers
Int J Clin Pharmacol Ther 2001 Mar;39(3):102-9.PMID:11396749DOI:10.5414/cpp39102.
Objective: To assess the pharmacokinetic and pharmacodynamic interactions of Emedastine difumarate, a new antihistamine drug and ketoconazole. Material: Twelve healthy Caucasian volunteers were administered Emedastine difumarate 4 mg oral capsules once daily for 10 consecutive days. From day 6 to day 10, ketoconazole 200 mg were co-administered twice daily. Methods: The effects of multiple ketoconazole administration on Emedastine kinetics were evaluated by comparing values obtained for pharmacokinetic parameters at steady state, with and without ketoconazole. C(ss,max), C(ss,min), tmax, AUCss, t(1/2) and Cl(ss)/F values, obtained after both treatments, were compared. Significant difference was defined as p < 0.05. QTc intervals from ECGs at baseline, after Emedastine treatment and after emedastine-ketoconazole co-treatment were statistically compared. Results: Emedastine steady state pharmacokinetics were slightly altered as a result of the ketoconazole co-treatment. AUCss rose by about 33% (increase ranging from 0.96 to 66.86, p < 0.001) and total clearance decreased by about 30% (ranging from 0.96 to 40.08, p < 0.001) with no change in the half-life. These events did not lead to relevant pharmacodynamic changes, i.e. maximum prolongation of the corrected QT interval (QTc) observed after 5 days co-treatment (day 10) was of about 4%. Rate and severity of anti-H 1 sedation episodes also did not increase on ketoconazole co-treatment. Conclusions: A moderate, but statistically significant interaction between Emedastine and ketoconazole was observed. Pharmacodynamic data indicate no increase in the QTc interval during concomitant therapy. This result is consistent with the multiple Emedastine metabolic pathways shown in man which supplement the metabolism by different enzymatic isoforms of CYP450. Concomitant treatment with Emedastine and ketoconazole in subjects with normal QT intervals can therefore, be undertaken without special precautions.
Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and second messenger studies
J Ocul Pharmacol 1994 Winter;10(4):653-64.PMID:7714409DOI:10.1089/jop.1994.10.653.
The antihistaminic agent, Emedastine, was tested for its ability to compete for [3H]pyrilamine, [3H]tiotidine and [3H]N-methyl histamine binding to rodent brain H1, H2 and H3 histamine receptors, respectively. Emedastine exhibited the highest affinity for H1-receptors (dissociation constant, Ki = 1.3 +/- 0.1 nM), and was considerably weaker at H2- (K1 = 49,067 +/- 11,113 nM) and H3-receptors (Ki = 12,430 +/- 1,282 nM). These data yielded ratios of 37744, 9562 and 4 for H2:H1, H3:H1 and H2:H3 receptor affinities, respectively, thus making Emedastine a very selective H1-receptor antagonist. The H1-selectivity of Emedastine was considerably superior to that of pyrilamine (H2:H1, H3:H1 and H2:H3 ratios of 11887, 12709 and 1, respectively). Similarly, the respective receptor affinity ratios for ketotifen (858, 1752, 0.5), levocabastine (420, 82, 5), pheniramine (430, 312, 1), chlorpheniramine (5700, 2216, 3) and antazoline (1163, 1110, 1) showed these antihistamines to be also markedly less H1-selective than Emedastine. The potency of Emedastine (IC50 = 1.44 +/- 0.3 nM) for antagonizing histamine-induced phosphoinositide turnover in human trabecular meshwork cells compared well with its binding affinity at the H1-receptor. These data indicate Emedastine to be a high affinity and high potency histamine antagonist with the highest selectivity for the H1-histamine receptor.
Effects of Emedastine and cetirizine, alone and with alcohol, on actual driving of males and females
J Psychopharmacol 2002 Mar;16(1):57-64.PMID:11949773DOI:10.1177/026988110201600104.
Emedastine is registered in its country of origin (Japan) as an antihistamine for the indication of seasonal allergic rhinitis. Further research on the drug's sedating properties was needed to secure its registration elsewhere. The present study was designed to compare the effects of Emedastine 2 mg and 4 mg twice daily after single and repeated doses, on actual driving performance versus those of cetirizine 10 mg once daily and placebo; and to determine how repeated doses of each drug interact with alcohol to affect driving. Each treatment was administered for 5 days to 19 healthy volunteers (nine men and ten women, aged 21-45 years) according to a four-period double-blind cross-over design. Driving performance was measured in a standardized test between 3 and 4 h after administration of the morning dose on days 1, 4 and 5. Alcohol, sufficient for achieving a blood alcohol concentration of 0.05 g/dl was given before driving on day 5 of each period. Both Emedastine doses similarly and significantly impaired driving in every test. The effects of cetirizine were less. They were significant over days 1, 4 and 5 combined, although not separately. Women were more impaired by both drugs. Alcohol increased driving impairment similarly in every condition. Subjects were only able to discriminate the sedating and impairing effects of the first dose of Emedastine 4 mg from placebo. Emedastine, in oral doses of 2 mg and 4 mg twice daily, is sedating and impairs driving. The drug could therefore constitute a traffic hazard and its users should be warned accordingly.