olopatadine-hydrochloride and Sneezing

Second-generation oral H1-antihistamines have become a mainstay of treatment for the symptoms of seasonal allergic rhinitis; however, the effect of olopatadine has not been widely reported to date.. To evaluate the efficacy of 2 oral H1-antihistamines, olopatadine and fexofenadine, in the treatment of the nasal symptoms of Japanese cedar pollinosis and their possible side effects.. This was a randomized, double-blind, placebo-controlled, crossover study conducted in an environmental exposure unit (EEU). Twenty volunteers suffering from Japanese cedar pollinosis were randomly divided into 3 groups and exposed to cedar pollen in the EEU with oral administration of olopatadine hydrochloride (5 mg), fexofenadine hydrochloride (60 mg), or placebo 1 hour prior to pollen exposure. Nasal symptoms, activity impairment, and subjective sleepiness were self-assessed during the study period. Attention was measured using the digit cancellation test. The trial was repeated after 4 and 7 weeks.. Compared with placebo, olopatadine significantly improved nasal symptoms and activity impairment during pollen exposure (P < .05). There was no significant relief of nasal discharge or nasal congestion with fexofenadine throughout the 5-hour exposure to cedar pollen. Furthermore, olopatadine significantly reduced nasal congestion during the first 2 hours, as well as sneezing and nasal discharge 4 hours after admission to the EEU compared with fexofenadine (P < .05). There was no significant difference in the effect on subjective sleepiness among the 3 groups, and all 3 agents had little effect on attention.. These findings suggest that olopatadine is more effective than placebo and fexofenadine in improving nasal symptoms of Japanese cedar pollinosis.

Topics: Adult; Allergens; Cryptomeria; Dibenzoxepins; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Motor Activity; Olopatadine Hydrochloride; Pollen; Rhinitis, Allergic, Seasonal; Sleep; Sneezing; Terfenadine; Treatment Outcome

The effects of three oral doses of a new compound KW 4679 thought to have both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volunteers with seasonal allergic rhinitis. Comparison of the effect of the treatments with either 2.5, 5 or 10 mg b.i.d. of KW 4679, 60 mg b.i.d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway resistance (NAR) was measured using active posterior rhinomanometry and the dose of grass pollen which caused a 200% increase in NAR was determined. The number of sneezes in the first 12 min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibited the skin weal response to histamine and grass pollen (P < 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induced skin weals was significantly greater than that of terfenadine (P = 0.001 and P = 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were effective in reducing sneeze counts (P < 0.001), though there were no significant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsiness whilst taking placebo. Slight and reversible rises in AST and ALT concentrations were observed; these were not considered clinically significant.

Topics: Adult; Airway Resistance; Cross-Over Studies; Dibenzoxepins; Double-Blind Method; Female; Humans; Male; Nasal Provocation Tests; Olopatadine Hydrochloride; Placebos; Rhinitis, Allergic, Seasonal; Skin Tests; Sleep Stages; Sneezing; Terfenadine

Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa.

Topics: Animals; Chlorpheniramine; Dibenzazepines; Dibenzoxepins; Drug Administration Schedule; Histamine H1 Antagonists; Imidazoles; Interleukin-4; Male; Nasal Mucosa; Olopatadine Hydrochloride; Rats; Rats, Inbred BN; Receptors, Histamine H1; RNA, Messenger; Sneezing; Time Factors; Toluene 2,4-Diisocyanate; Transcription, Genetic; Up-Regulation

The present study was undertaken to investigate the pathological role of substance P in allergic nasal symptoms in rats. The topical application of substance P caused an increase in the incidence of sneezing and nasal rubbing in a dose-dependent fashion, and at a dose of 30 nM/site it showed a significant effect. L-732,138, a tachykinin NK(1) receptor antagonist, at doses of 3 and 10 mg/kg showed a significant inhibition of the nasal signs induced by exogenous substance P in rats. In addition, L-732,138 also showed a significant inhibition of nasal behavior induced by antigen in actively sensitized rats at the same dose. On the other hand, histamine H(1) receptor antagonists, such as cyproheptadine, epinastine and olopatadine had no effect on the nasal behaviors induced by exogenous substance P, even at higher doses, indicating that exogenous substance P does not cause the degranulation of mucosal mast cells in the rat. Moreover, all the histamine H(1) receptor antagonists showed the dose-dependent inhibition of the nasal signs induced by antigen in actively sensitized rats, which revealed that the inhibition of these drugs was exhibited through the antagonistic effect on histamine H(1) receptors. Therefore, from these results, it is reasonable to conclude that substance P released from the nasal mucosa through the activation of tachykinin NK(1) receptors during the antigen antibody reaction plays an important role in allergic nasal symptoms.

Topics: Animals; Antigens; Cyproheptadine; Dibenzazepines; Dibenzoxepins; Dose-Response Relationship, Drug; Electroencephalography; Histamine H1 Antagonists; Hypersensitivity; Imidazoles; Male; Neurokinin-1 Receptor Antagonists; Olopatadine Hydrochloride; Rats; Rats, Wistar; Sneezing; Substance P; Tryptophan

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.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Capsaicin; Dibenzoxepins; Guinea Pigs; Male; Olopatadine Hydrochloride; Sneezing; Tachykinins