The Effect of KW-4679, an Antiallergic Drug, on Experimental Allergic Rhinitis in Guinea Pigs: Effects on Nasal Blockage

Abstract

ABSTRACT-Weinvestigated the effect of KW-4679 (Z-11-(dimethylaminopropyliden)-6,11-dihydrodibenzoxepin-2-acetic acid hydrochloride), an antiallergic agent, on the nasal blockage induced by antigen challenge into the nostrils of actively sensitized guinea pigs. The change of the nasal cavity volume caused by nasal mucosal swelling after antigen challenge was measured by acoustic rhinometry. Oral administration of KW-4679 (0.01-10 mg/kg) significantly inhibited the decrease in the nasal cavity volume at 10 min, 30 min and 6 hr after antigen challenge. Ketotifen (1-10 mg/kg, p.o.) also inhibited the decrease in the nasal cavity volume after antigen challenge. These results indicate that KW-4679 may be useful for the treatment of allergic rhinitis.

Effects of Olopatadine Hydrochloride on the Increase of Histamine and Peptide-Leukotrienes Concentrations in Nasal Lavage Fluid Following the Antigen-Antibody Reaction in Actively Sensitized Guinea Pigs

“…We confirmed that olopatadine significantly inhibited the sneeze and nasal rubbing responses in the actively sensitized guinea pig (T. Kaise et al, unpublished data) as well as in the passively sensitized animal (7). In addition, we have reported that chlorpheniramine, a classic histamine H1-antagonist, prominently inhibited the sneeze and nasal rubbing responses in the actively sensitized animal, while pranlukast, a LT-receptor antagonist, and seratrodast failed to inhibit these responses (11).…”

“…The previous in vitro studies demonstrated that olopatadine inhibited the mediator release from several inflammatory cells (5,6). Kaise et al reported that olopatadine inhibited the sneeze and nasal rubbing responses and the nasal blockage caused by antigen challenge in sensitized guinea pigs (7,8). Moreover, olopatadine has been shown to be useful for the treatment of allergic rhinitis in human patients (9).…”

“…Active sensitization was performed as previously described by Kaise et al (8). Briefly, male Hartley guinea pigs (Japan SLC, Shizuoka), weighing 251 -300 g (4 weeks of age), were intraperitoneally injected with DNP-Ascaris (3.12 mg protein) and aluminium hydroxide (1 mg) 4 times at 2-week intervals, followed by inhalation of DNP-Ascaris (15.6 mg protein/ ml saline, for 3 min), repeated every day for 5 days, beginning 10 days after the fourth intraperitoneal injection.…”

“…Nasal cavities were perfused with 3 ml of saline for 10 min before (pre) and at various time points after the challenge, and NALF was collected. Olopatadine at 10 mg/kg, a dose exhibiting the inhibitory effect on experimental allergic rhinitis (8), was orally administrated 1 h before the antigen challenge. In the control and the sham group, the vehicle (distilled water) was given instead of the drug.…”

Involvement of Neuropeptides in the Allergic Nasal Obstruction in Guinea Pigs

“…In sensitized guinea pigs, LY303870 or SR48968 was intravenously administered 30 min before, and CGRP(8 -37) was intravenously given 2 min before the intranasal antigen challenge. The nasal cavity volume was measured before and until 6 h after the challenge, since our previous study demonstrated that the decreases in the nasal cavity volume developed till 6 h after the antigen challenge in sensitized guinea pigs (17).…”