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.