piperidines and Sneezing

In allergic rhinitis, a nasal H1-antihistamine spray seems to be well suited for usage on an as-needed basis, because it has a quick onset of action, and many patients prefer to take medicine only when they have symptoms. It is a prerequisite, however, that nasal hypersecretion during a rhinitis episode does not significantly reduce the efficacy of intranasal treatment by washing away the drug before it reaches the H1-histamine receptors. In order to investigate this problem, we have induced nasal hypersecretion with a methacholine challenge in one experiment and in four experiments we have washed the nasal cavities 0.5 min. before, 5 min. before, 0.5 min. after and 5 min. after intranasal use of the H1-antagonist, levocabastine. The symptom response to a subsequent histamine challenge was used as the effect parameter. Levocabastine reduced the number of histamine-induced sneezes with 81% (p < 0.0001) and the secretion weight with 62% (p < 0.001) compared with placebo. Neither methacholine-induced hypersecretion nor washing the nose with saline reduced the efficacy of the antihistamine spray. We conclude that experimentally induced nasal hypersecretion does not reduce the efficacy of the antihistamine spray, and probably the same applies to rhinorrhea during an acute episode of allergic rhinitis.

Topics: Administration, Intranasal; Adult; Analysis of Variance; Double-Blind Method; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Methacholine Chloride; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Piperidines; Rhinitis; Sneezing; Statistics, Nonparametric

The effect of intranasal administration of levocabastine, a new selective H1-receptor antagonist, was investigated in a nasal provocation test (NPT) performed with allergens. The NPT allowed a quantitative estimation of the nasal allergic threshold (concentration of allergen necessary to trigger the reaction). In addition, the intensity of the three major rhinitis symptoms (obstruction, rhinorrhea and sneezing) was determined. Twelve adult patients, allergic to grass pollen, underwent a first NPT without pretreatment ('initial NPT'); the NPT was then repeated after the single intranasal administration of either placebo, 8 mg disodium cromoglycate (DSCG) or 0.2 mg levocabastine in a double-blind random order. The NPTs gave reproducible results since both the threshold and symptom intensities were similar in the initial NPT and in the NPT performed after placebo. The reaction threshold increased in 8/12 patients after DSCG (0.05 less than P less than 0.1) and in 9/12 patients after levocabastine (P less than 0.05). Levocabastine clearly inhibited rhinorrhea (P less than 0.001) and sneezing (P less than 0.02) but did not influence the nasal obstruction. DSCG inhibited rhinorrhea only (P less than 0.01). The intranasal administration of levocabastine might be useful in the treatment of allergic rhinitis.

Topics: Administration, Inhalation; Adolescent; Adult; Allergens; Child; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Nasal Mucosa; Nasal Provocation Tests; Piperidines; Sneezing

The present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertussis toxin. Five days later, they were boosted by a subcutaneous injection of ovalbumin into the back. From day 18 after the first immunization to day 39, intranasal sensitization with ovalbumin was performed every day and the severity of allergic rhinitis was observed by measuring nasal allergic responses and total IgE levels. It was found that the intranasal administration of antigen caused a significant increase of nasal sneezing and rubbing from day 25 to day 39 both in sensitized HDC-KO and wild-type mice. In addition, a significant elevation of total IgE levels in serum was also found both in sensitized HDC-KO and wild-type mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin NK(1) receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the dose-dependent inhibition of nasal allergic responses induced by antigen in both HDC-KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and 10 mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a dose-related reduction of the nasal allergic responses induced by antigen in sensitized wild-type mice. On the other hand, they had no effects on the nasal signs induced by antigen in HDC-KO mice. From these results, it was revealed that substance P induces nasal allergic responses in the mouse model of chronic allergic rhinitis through the activation of tachykinin NK(1) receptors. Therefore, it can be concluded that not only histamine, but also substance P and prostaglandin D(2), participated in the nasal allergic responses induced by antigen in mice.

Topics: Animals; Behavior, Animal; Chlorpheniramine; Histamine H1 Antagonists; Histidine Decarboxylase; Hydantoins; Immunization; Immunoglobulin E; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurokinin-1 Receptor Antagonists; Ovalbumin; Piperidines; Receptors, Immunologic; Receptors, Prostaglandin; Rhinitis, Allergic, Seasonal; Sneezing; Substance P