Effect of olopatadine hydrochloride, an anti-histamine drug, on rhinitis induced by intranasal instillation of toluene-2,4-diisocyanate in rats.
The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. In patients with AR, levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) increase. Olopatadine hydrochloride (olopatadine) is an anti-allergic agent with histamine H1 receptor antagonistic action. To investigate whether olopatadine has an effect on inflammatory reactions, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as an animal model of nasal allergy. Nasal allergy signs (sneezing, rhinorrhea and inflammation) were induced after TDI challenge. Amounts of NGF and VEGF in the nasal lavage fluid increased. Olopatadine reduced nasal allergy signs and inhibited increases in NGF and VEGF. These findings suggest that the increases in NGF and VEGF production are involved in the mechanism responsible for nasal allergy signs in TDI-challenged rats. Other histamine H1 receptor antagonists did not inhibit and instillation of histamine did not increase TDI-induced NGF and VEGF production. Therefore, olopatadine appears to exert additional biological effects other than its blockade of the histamine H(1) receptor. These results suggest that suppression of neurogenic inflammatory reactions might be partially involved in the improvement of allergy signs after treatment with olopatadine.
Tamura
Tadafumi
T
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. tadafumi.tamura@kyowa.co.jp
Komai
Masato
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D003990:Dibenzoxepins / Q000494:pharmacology*; D004195:Disease Models, Animal; D006632:Histamine / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology; D020932:Nerve Growth Factor / Q000378:metabolism*; D000069605:Olopatadine Hydrochloride; D051381:Rats; D017207:Rats, Sprague-Dawley; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000378:metabolism*; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D039563:Histamine H1 Antagonists, Non-Sedating; D042461:Vascular Endothelial Growth Factor A; D014051:Toluene 2,4-Diisocyanate; D000069605:Olopatadine Hydrochloride; D006632:Histamine; D020932:Nerve Growth Factor