ABSTRACT-To investigate the possible inhibitory effect of olopatadine hydrochloride (olopatadine), an antiallergic drug, on the tachykinin-mediated nasal responses, we examined the effect of olopatadine on the sneezing and the nasal rubbing responses induced by intranasal capsaicin challenge in guinea pigs. Olopatadine (10 mg/kg, p.o.) inhibited the sneezing response by 57% without affecting the nasal rubbing one. The antihistamines chlorpheniramine and clemastine did not affect the responses. Morphine caused the inhibition of both responses, which was antagonized by naloxone. These results suggest that olopatadine inhibits the sneezing response by the inhibition of the tachykinin release and not by its antihistaminic action.

ABSTRACT-The purposes of the present study were i) to determine whether neuropeptides induce the nasal obstruction in guinea pigs, and ii) to examine the possible involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal cavity volume was determined by acoustic rhinometry as an index of nasal obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30 min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK 1-receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and CGRP(8 -37) (50 nmol / kg), a CGRP1-receptor antagonist, administered intravenously before the intranasal application of the neuropeptides, inhibited the responses induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen challenge caused nasal obstruction. The response was biphasic and consisted of the early phase response (EPR) and the late phase response (LPR), which developed 30 min and 6 h, respectively, after the antigen challenge. Intravenous administration of LY303870 (1 mg / kg) before the antigen challenge inhibited the EPR, while those of SR48968 (1 mg /kg) and CGRP(8 -37) (50 nmol/ kg) inhibited the LPR. The present results suggest that neuropeptides are involved in the allergic nasal obstruction.Keywords: Nasal obstruction, Substance P, Neurokinin A, Calcitonin gene-related peptide Nasal obstruction is one of the major symptoms of allergic rhinitis. The previous studies in allergic rhinitis patients demonstrated that classical histamine H1-receptor antagonists such as chlorpheniramine, hydroxyzine and clemastine were not effective in the treatment of nasal obstruction (1, 2), suggesting an involvement of mediators other than histamine in the pathogenesis of the nasal obstruction. The involvement of peptide leukotrienes (p-LTs) and thromboxane A2 has been suggested as pranlukast (3), a p-LTs receptor antagonist, and ramatroban (4), a thromboxane A2-receptor antagonist, showed clinical efficacy in the treatment of nasal obstruction.There are some results suggesting the involvement of neuropeptides in the pathogenesis of nasal obstruction, although the effectiveness of an antagonist against neuropeptide receptor has not been elucidated in humans. Nerve fibers containing neuropeptides such as substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) have been found in the human nasal mucosa (5, 6).Their receptors, that is, tachykinin NK 1, tachykinin NK2 and CGRP1 receptors, respectively, have also been shown to exist in human nasal mucosa (5, 6). Moreover, the intranasal administration of SP, NKA or CGRP has been reported to cause nasal obstruction in humans (7 -9).The purposes of the present study were i) to determine the effects of SP, NKA and CGRP on the nasal cavity volume in guinea pigs and ii) to examine the possible involvement of the neuropeptides i...

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We have investigated the effect of oxatomide, an antiallergic agent, on experimental allergic rhinitis in sensitized guinea pigs. Oxatomide (1 and 10 mg/kg, p.o.) significantly inhibited the sneeze response and nasal rubbing after antigen challenge. Oxatomide (10 and 30 mg/kg) reduced the increase in nasal vascular permeability induced by the antigen-antibody reaction. The decreases in nasal cavity volume caused by nasal mucosal swelling 10 min, 30 min and 6 hr after antigen challenge were significantly inhibited by oxatomide (30 mg/kg). These results indicate that oxatomide inhibits the experimental allergic rhinitis in guinea pigs.