Гистамин является одним из наиболее важных медиаторов, который высвобождается из тучных клеток и базофилов при аллергической патологии. Основными средствами для лечения аллергии являются Н1-антигистаминные препараты II поколения (АГ II), которые представляют собой высокоспецифичные агонисты Н1-рецепторов длительного действия. Исследования последних лет показали, что некоторые АГ II помимо антигистаминной активности имеют противовоспалительную активность, не связанную с блокадой Н1-рецепторов, а обусловленную блокированием высвобождения медиаторов воспаления базофилами, тучными клетками, уменьшением экспрессии молекул адгезии и угнетением привлечения в зону воспаления клеток аллергического ответа. Таким образом, антигистаминные препараты II поколения могут подавлять развитие поздней фазы и предотвращать хронизацию аллергического воспаления. Данная статья представляет собой обзор имеющейся на данный момент информации по антигистаминному, противовоспалительному и противоаллергическому профилю дезлоратадина.
Histamine is one of the most important mediators that are released from mast cells and basophils in allergic diseases. The main means for the treatment of allergies are H1-antihistamines second generation, which are highly specific agonists H1 receptor for long periods. Recent studies have shown that some of H1-antihistamines in addition to the second-generation antihistamine activity have anti-inflammatory activity that is not related to the blockade of H1-receptors, and blocking due to the release of inflammatory mediators by basophils, mast cells, a decrease in the expression of adhesion molecules and inhibition of attraction in the area of inflammation cells allergic response. Thus, the second-generation antihistamines may inhibit the development of late phase and prevent chronization allergic inflammation. This article provides an overview of the currently available information on antihistamines, anti-inflammatory and antiallergic profile of desloratadine.
1. Akdis CA, Simons FER. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol 2006; 533: 69–76.
2. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy 2008; 94: 67–82.
3. Schneider E, Rolli-Derkinderen M, Arock M, Dy M. Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol 2002; 23: 255–63.
4. Baena-Cagnani CE. Desloratadine activity in concurrent seasonal allergic rhinitis and asthma. Allergy 2001; 56: 21–7.
5. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1418–26.
6. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008; 7: 41–53.
7. Das AK, Yoshimura S, Mishima R et al. Stimulation of histamine H1 receptor up-regulates histamine H1-receptor itself through activation of receptor gene transcription. J Pharmacol Sci 2007; 103: 374–82.
8. Simons FER. Advances in H1-antihistamines. N Engl J Med 2004; 351: 2203–17.
9. Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R. Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 2001; 60: 1133–42.
10. Canonica GW, Blaiss M. Antihistaminic, anti-Inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. WAO Journal 2011; 4: 47–53.
11. Greasley PJ, Clapham JC. Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing? Eur J Pharmacol 2006; 553: 1–9.
12. Scadding G. Predicting and establishing the clinical efficacy of a histamine H1- receptor antagonist: desloratadine, the model paradigm. Clin Drug Invest 2005; 25: 153–64.
13. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002; 32: 489–98.
14. Costa T, Cotecchia S. Historical review: negative efficacy and the constitutive activity of G-protein-coupled receptors. Trends Pharmacol Sci 2005; 26: 618–24.
15. De Ligt RA, Kourounakis AP, IJzerman AP. Inverse agonism at G-protein-coupled receptors: (patho) physiological relevance and implications for drug discovery. Br J Pharmacol 2000; 130: 1–12.
16. Bakker RA, Wieland K, Timmerman H, Leurs R. Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H1 receptor antagonists. Eur J Pharmacol 2000; 387: R5–R7.
17. Bousquet J, Khaltaev N, Cruz AA et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy 2008; 63 (Suppl. 86): 8–160.
18. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. Allergy 2009; 64: 1427–43.
19. Bousquet J, Bachert C, Canonica GW et al. ACCEPT-1 Study Group. Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN study. Allergy 2009; 64: 1516–23.
20. Canonica GW, Tarantini F, Compalati E, Penagos M. Efficacy of desloratadine in the treatment of allergic rhinitis: a meta-analysis of randomized, double-blind, controlled trials. Allergy 2007; 62: 359–66.
21. Monroe E, Finn A, Patel P et al. Desloratadine Urticaria Study Group. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomised, placebo-controlled trial. J Am Acad Dermatol 2003; 48: 535–41.
22. Ortonne J-P, Grob J-J, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol 2007; 8: 37–42.
23. Ring J, Hein R, Gauger A et al. Desloratadine Study Group. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Int J Dermatol 2001; 40: 72–6.
24. Siebenhaar F, Degener F, Zuberbier T et al. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol 2009; 123: 672–9.
25. Zuberbier T, Canonica GW. Desloratadine significantly decreases total symptoms scores in subjects with persistent allergic rhinitis: ACCEPT-2 study in collaboration with GA2LEN. Ann Allergy Asthma Immunol 2009; 102: A119.
26. Anthes JC, Gilchrest H, Richard C Eckel S et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor. Eur J Pharmacol 2002; 449: 229–37.
27. Wu R-L, Anthes JC, Kreutner W et al. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-кB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol 2004; 135: 313–8.
28. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006; 24: 147–74.
29. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111 (Suppl.): S460–S475.
30. Lebel B, Bousquet J, Czarlewski W, Campbell AM. Loratadine (L) reduces RANTES release by an epithelial cell line. J Allergy Clin Immunol 1997; 99: S444. Abstract 1802.
31. Kowalski ML, Lewandowska A, Wozniak J et al. Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine. Allergy 2005; 60: 80–5.
32. Wang YH, Taché Y, Harris AG et al. Desloratadine prevents compound 48/80-induced mast cell degranulation: visualization using a vital fluorescent dye technique. Allergy 2005; 60: 117–24.
33. Genovese A, Patella V, De Crescenzo G et al. Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRl+ cells. Clin Exp Allergy 1997; 27: 559–67.
34. Lippert U, Kru¨ger-Krasagakes S, Mo¨ller A et al. Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines. Exp Dermatol 1995; 4 (Part. 2): 272–6.
35. Weller K, Maurer M. Desloratadine inhibits human skin mast cell activation and histamine release. J Invest Dermatol 2009; 129: 2723–6.
36. Molet S, Gosset P, Lassalle P et al. Inhibitory activity of loratadine and descarboxyethoxyloratadine on histamine-induced activation of endothelial cells. Clin Exp Allergy 1997; 27: 1167–74.
37. Vignola AM, Crampette L, Mondain M et al. Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells. Allergy 1995; 50: 200–3.
38. Traidl-Hoffmann C, Mu¨nster I, Ring J, Behrendt H. Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: implications for anti-inflammatory activity of antihistamines. Int Arch Allergy Immunol 2006; 140: 315–20.
________________________________________________
1. Akdis CA, Simons FER. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol 2006; 533: 69–76.
2. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy 2008; 94: 67–82.
3. Schneider E, Rolli-Derkinderen M, Arock M, Dy M. Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol 2002; 23: 255–63.
4. Baena-Cagnani CE. Desloratadine activity in concurrent seasonal allergic rhinitis and asthma. Allergy 2001; 56: 21–7.
5. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1418–26.
6. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008; 7: 41–53.
7. Das AK, Yoshimura S, Mishima R et al. Stimulation of histamine H1 receptor up-regulates histamine H1-receptor itself through activation of receptor gene transcription. J Pharmacol Sci 2007; 103: 374–82.
8. Simons FER. Advances in H1-antihistamines. N Engl J Med 2004; 351: 2203–17.
9. Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R. Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 2001; 60: 1133–42.
10. Canonica GW, Blaiss M. Antihistaminic, anti-Inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. WAO Journal 2011; 4: 47–53.
11. Greasley PJ, Clapham JC. Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing? Eur J Pharmacol 2006; 553: 1–9.
12. Scadding G. Predicting and establishing the clinical efficacy of a histamine H1- receptor antagonist: desloratadine, the model paradigm. Clin Drug Invest 2005; 25: 153–64.
13. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002; 32: 489–98.
14. Costa T, Cotecchia S. Historical review: negative efficacy and the constitutive activity of G-protein-coupled receptors. Trends Pharmacol Sci 2005; 26: 618–24.
15. De Ligt RA, Kourounakis AP, IJzerman AP. Inverse agonism at G-protein-coupled receptors: (patho) physiological relevance and implications for drug discovery. Br J Pharmacol 2000; 130: 1–12.
16. Bakker RA, Wieland K, Timmerman H, Leurs R. Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H1 receptor antagonists. Eur J Pharmacol 2000; 387: R5–R7.
17. Bousquet J, Khaltaev N, Cruz AA et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy 2008; 63 (Suppl. 86): 8–160.
18. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. Allergy 2009; 64: 1427–43.
19. Bousquet J, Bachert C, Canonica GW et al. ACCEPT-1 Study Group. Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN study. Allergy 2009; 64: 1516–23.
20. Canonica GW, Tarantini F, Compalati E, Penagos M. Efficacy of desloratadine in the treatment of allergic rhinitis: a meta-analysis of randomized, double-blind, controlled trials. Allergy 2007; 62: 359–66.
21. Monroe E, Finn A, Patel P et al. Desloratadine Urticaria Study Group. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomised, placebo-controlled trial. J Am Acad Dermatol 2003; 48: 535–41.
22. Ortonne J-P, Grob J-J, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol 2007; 8: 37–42.
23. Ring J, Hein R, Gauger A et al. Desloratadine Study Group. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Int J Dermatol 2001; 40: 72–6.
24. Siebenhaar F, Degener F, Zuberbier T et al. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol 2009; 123: 672–9.
25. Zuberbier T, Canonica GW. Desloratadine significantly decreases total symptoms scores in subjects with persistent allergic rhinitis: ACCEPT-2 study in collaboration with GA2LEN. Ann Allergy Asthma Immunol 2009; 102: A119.
26. Anthes JC, Gilchrest H, Richard C Eckel S et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor. Eur J Pharmacol 2002; 449: 229–37.
27. Wu R-L, Anthes JC, Kreutner W et al. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-кB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol 2004; 135: 313–8.
28. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006; 24: 147–74.
29. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111 (Suppl.): S460–S475.
30. Lebel B, Bousquet J, Czarlewski W, Campbell AM. Loratadine (L) reduces RANTES release by an epithelial cell line. J Allergy Clin Immunol 1997; 99: S444. Abstract 1802.
31. Kowalski ML, Lewandowska A, Wozniak J et al. Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine. Allergy 2005; 60: 80–5.
32. Wang YH, Taché Y, Harris AG et al. Desloratadine prevents compound 48/80-induced mast cell degranulation: visualization using a vital fluorescent dye technique. Allergy 2005; 60: 117–24.
33. Genovese A, Patella V, De Crescenzo G et al. Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRl+ cells. Clin Exp Allergy 1997; 27: 559–67.
34. Lippert U, Kru¨ger-Krasagakes S, Mo¨ller A et al. Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines. Exp Dermatol 1995; 4 (Part. 2): 272–6.
35. Weller K, Maurer M. Desloratadine inhibits human skin mast cell activation and histamine release. J Invest Dermatol 2009; 129: 2723–6.
36. Molet S, Gosset P, Lassalle P et al. Inhibitory activity of loratadine and descarboxyethoxyloratadine on histamine-induced activation of endothelial cells. Clin Exp Allergy 1997; 27: 1167–74.
37. Vignola AM, Crampette L, Mondain M et al. Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells. Allergy 1995; 50: 200–3.
38. Traidl-Hoffmann C, Mu¨nster I, Ring J, Behrendt H. Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: implications for anti-inflammatory activity of antihistamines. Int Arch Allergy Immunol 2006; 140: 315–20.
Авторы
Н.И.Ильина, К.С.Павлова*
ФГБУ Государственный научный центр Институт иммунологии ФМБА России. 115478, Россия, Москва, Каширское ш., д. 24, корп. 2
*ksenimedical@gmail.com
________________________________________________
N.I.Ilyina, K.S.Pavlova*
Institute of Immunology. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 24, korp. 2
*ksenimedical@gmail.com