Effects of Fexofenadine Hydrochloride in a Guinea Pig Model of Antigen-Induced Rhinitis

Abstract

Allergic rhinitis is an inflammatory disease of the nasal mucosa, induced by histamine, leukotrienes, and other substances released from mast cells. Fexofenadine hydrochloride, the active metabolite of terfenadine, is a novel, nonsedating antiallergic drug having H₁ receptor antagonistic activity. Fexofenadine is effective for the treatment of allergic rhinitis. However, its mechanism of action in attenuating nasal congestion has not yet been elucidated. Therefore, we first examined the effects of fexofenadine on a guinea pig model of antigen-induced rhinitis. We also evaluated the effects of mepyramine, zafirlukast and ramatroban in this model; these drugs are an H₁ receptor antagonist, a selective leukotriene antagonist and a selective thromboxane antagonist, respectively. Rhinitis was induced by ovalbumin (OVA) instillation into the nasal cavity of animals that had been sensitized by two earlier OVA injections (s.c. and i.p.). The nasal airway resistance was measured for 45 min after the challenge. Fexofenadine hydrochloride (20 mg/kg) and terfenadine (20 mg/kg) administered orally 70 min prior to the challenge significantly inhibited (fexofenadine, p < 0.001, terfenadine, p < 0.05) the increase in nasal airway resistance. Ramatroban (30 mg/kg) administered orally 60 min prior to the challenge also significantly inhibited (p < 0.05) the increase in nasal airway resistance. In contrast, mepyramine (3 mg/kg i.v.) and zafirlukast (3 mg/kg p.o.) failed to reduce the increase in nasal airway resistance. These results suggest that thromboxane may be involved in the increase in the nasal airway resistance in this model. Accordingly, fexofenadine may reduce the increase in nasal airway resistance by inhibiting the release of chemical mediators, including thromboxane, that are involved in the increase in nasal airway resistance in this model.

New Evidence of H₁-Receptor Independent COX-2 Inhibition by Fexofenadine HCl in vitro

“…In vitro studies have shown that FEX inhibited the production of metalloproteinase (MMP)-2 and MMP-9, as well as MMP mRNA expression and NF-B activation from both nasal polypderived fibroblasts and nasal mucosal fibroblasts in response to tumor necrosis factor-␣ stimulation [27] . FEX also inhibited thymus-and activation-regulated chemokine levels in peripheral blood leukocytes [29] and blocked TX release, thus reducing the increase of nasal airway resistance in a guinea pig model of antigen-induced rhinitis [30] . In our recently published study, it was shown that FEX inhibited the production of arachidonic acid metabolites LTC 4 -LTD 4 -LTE 4 and PGE 2 in cultured human monocytes, but appeared to have no effect on 5-lipoxygenase [17] .…”

Establishment of a new animal model of allergic rhinitis with biphasic sneezing by intranasal sensitization with Staphylococcal enterotoxin B

“…Terfenadine is an H1 receptor antagonist. It has been reported that terfenadine at the above doses significantly inhibits allergic inflammation of the nasal cavity induced by histamine in guinea pigs (16).…”

Anti‐allergic effects of total bakkenolides from Petasites tricholobus in ovalbumin‐sensitized rats

“…Then, local sensitization was performed every day. From day 14 to day 27, the egg albumin in physiological saline (1 mg/mL, 10 µL) was dropped into the bilateral nasal cavities with a micropipette (Sakairi et al , 2005; McLeod et al , 2002). On day 20, blood was drawn from all groups via the orbit for the assessment of total immunoglobulin E (IgE).…”