piperidines and Rhinitis--Allergic--Perennial

Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Benzimidazoles; Butyrophenones; Cyproheptadine; Fluticasone; Histamine H1 Antagonists; Humans; Omalizumab; Phthalazines; Piperidines; Pregnenediones; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Bepotastine besilate 1.5% is a newly approved second-generation topical antihistamine indicated for the pruritus associated with allergic conjunctivitis. In Japan, the oral formulation is approved to manage pruritus associated with allergic rhinitis and urticaria.. Bepotastine is a piperidine derivative that antagonizes H1 receptors with high selectivity. It has been labeled a dual-acting or multiple-acting antiallergic medication, because it inhibits histamine at H1 receptors and stabilizes mast cells to prevent histamine release. Bepotastine may also have other immunoactive properties, such as inhibition of eosinophil migration, interleukin-5 (IL-5), leukotrienes (e.g., LTB4) and platelet-activating factor (PAF). Human clinical trials demonstrate the efficacy and safety of systemic and ophthalmic bepotastine for pruritus relief, limited penetration across the blood-brain-barrier and kinetics suitable for twice-daily administration.. Bepotastine besilate 1.5% ophthalmic solution is a safe and effective treatment option for allergic conjunctivitis associated pruritus. Side-effect profile is similar to other ocular antihistamine agents. Additional comparative-effectiveness studies would further advance its clinical use. Oral bepotastine is a safe and effective treatment option approved in Japan for allergic rhinitis, urticaria and pruritus associated with skin diseases.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Pyridines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines development group examined the properties of oral H(1)-antihistamines and made proposals about an 'optimal' drug. Several criteria should be met by oral H(1)-antihistamines in terms of their pharmacological, and clinical efficacy and safety profiles.. Bilastine, a new H(1)-antihistamine, has been approved in 28 European countries for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. To determine its potential place in therapy in the treatment of allergic rhinitis, this manuscript examines whether bilastine meets the criteria defined in the European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for oral H(1)-antihistamines.. The optimal properties of oral H(1)-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria.. Bilastine is a potent inhibitor of the histamine H(1) receptor. Data from preclinical studies have confirmed its selectivity for the histamine H(1) receptor over other receptors, and demonstrated antihistaminic properties in vitro and in vivo. Bilastine does not interfere with the cytochrome P450 system and is devoid of cardiac side effects. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. In large pivotal randomized, placebo-controlled trials (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy than placebo and comparable to that of cetirizine and desloratadine. Moreover, bilastine was shown to improve quality of life, an important outcome of RCTs in allergic diseases. There were no significant changes in laboratory tests, electrocardiograms or vital signs. A potential limitation of this assessment of bilastine is that it is a literature-based review and the findings are dependent upon the quality of the published evidence.. Bilastine meets current EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

Topics: Adolescent; Adult; Anti-Allergic Agents; Asthma; Benzimidazoles; Child; Humans; Piperidines; Practice Guidelines as Topic; Rhinitis, Allergic, Perennial

Topics: Alzheimer Disease; Animals; Asthma; Dermatitis, Atopic; Drug Design; Enzyme Inhibitors; Humans; Intramolecular Oxidoreductases; Leukodystrophy, Globoid Cell; Lipocalins; Muscular Dystrophies; Niacinamide; Piperidines; Pulmonary Disease, Chronic Obstructive; Pyrazoles; Pyrimidines; Rhinitis, Allergic, Perennial; Spinal Cord Injuries; Thiazoles

Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials.

Topics: Area Under Curve; Benzimidazoles; Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Urticaria

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Topics: Animals; Automobile Driving; Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria; Wakefulness

This application claims dual receptor specificity antihistamines, active as H(1) and H(3) antagonists, which additionally have a long duration of action that renders them suitable for once daily administration via inhalation for the treatment of allergic rhinitis. The compounds lack CNS penetration and have a high affinity for both histamine receptors.

Topics: Animals; Histamine H1 Antagonists; Histamine H3 Antagonists; Humans; Naphthalenes; Patents as Topic; Phthalazines; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship

H1 antihistamines constitute one of the main references for the treatment of allergic rhinitis. Classically, these drugs have been considered effective in controlling sneezing, rhinorrhea and itching, though they have not been regarded as particularly effective in application to nasal obstruction. The most recent studies, involving second-generation H1 antihistamines (desloratadine, fexofenadine, levocetirizine, rupatadine), have shown these drugs to offer effects upon nasal obstruction significantly superior to those of placebo. The present review examines the effect of bilastine, a new, potent and highly specific H1 antihistamine without sedative effects or cardiac toxicity, upon nasal obstruction. The analysis of the data from the different clinical trials indicates that in patients with allergic rhinitis, the effect of bilastine upon nasal obstruction is superior to that of placebo and similar to that of other second-generation H1 antihistamines, manifesting within 24 hours after the start of treatment.

Topics: Benzimidazoles; Clinical Trials as Topic; Histamine H1 Antagonists; Humans; Nasal Obstruction; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The evaluation of quality of life (QoL) and its modification through therapeutic interventions has become a prioritary concern in recent years and a requirement on the part of regulatory agencies for the authorization of new drugs. In clinical studies of allergic disorders, particularly allergic rhinitis and urticaria, different types of generic questionnaires have been used - especially disease specific instruments such as the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) or skin disease specific tools such as the Dermatology Life Quality Index (DLQI). Throughout its clinical development, bilastine has been shown to be more effective than placebo and at least as effective as cetirizine, levocetirizine, fexofenadine or desloratadine in controlling the symptoms of seasonal allergic rhinitis and chronic urticaria. QoL has been studied as a secondary objective in three allergic rhinitis clinical trials, using the RQLQ, in a total of 2335 patients. Likewise, in chronic urticaria, QoL has been evaluated using the DLQI in a total of 525 patients, versus levocetirizine and placebo. The improvement in the QoL parameters in these studies (RQLQ or DLQI domains) at all times proved proportional to the symptoms improvement. In general, the data obtained relating to changes in QoL are concordant with the mean global visual analog scale (VAS in mm) values and their changes, from the beginning until the end of the treatment period, for all of the trials, for bilastine and all its comparators.

Topics: Benzimidazoles; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Ocular symptoms often accompany allergic rhinitis and can be as or even more bothersome for the patient than the actual nasal symptoms. Ocular manifestations of allergic rhinoconjunctivitis may result from both direct allergen-mediated mast cell stimulation on the surface of the eye and naso-ocular reflexes--histamine being one of the mediators of symptoms onset. An H1 antihistamine would be the first line treatment for allergic conjunctivitis. Since allergic conjunctivitis is always (or almost always) accompanied by nasal symptoms, a second-generation H1 antihistamine administered via oral route is the drug of choice for jointly managing both the nasal and the ocular symptoms--minimizing the impact of the effects inherent to first-generation H, antihistamine, including particularly drowsiness. Bilastine is a new H1 antihistamine with an excellent safety profile, developed for the treatment of allergic rhinoconjunctivitis and urticaria, with potency similar to that of cetirizine and desloratadine, and superior to that of fexofenadine. This new drug has been shown to be effective in controlling the ocular symptoms of allergic rhinoconjunctivitis.

Topics: Benzimidazoles; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Immunoglobulin E; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Oral bepotastine is a second-generation histamine H(1) receptor antagonist that also suppresses some allergic inflammatory processes. Numerous short- and long-term clinical trials and surveillance studies have shown that twice-daily bepotastine is an effective and generally well tolerated antihistamine in the treatment of patients with allergic rhinitis, chronic urticaria or pruritus associated with skin conditions (eczema/dermatitis, prurigo or pruritus cutaneus). Bepotastine 20 mg/day was significantly more effective than terfenadine 120 mg/day in patients with perennial allergic rhinitis, as evaluated by the final global improvement rating and several other endpoints in a phase III trial. In phase III trials in patients with chronic urticaria, bepotastine 20 mg/day was more effective than placebo in improving levels of itching and eruption, and as effective as terfenadine 120 mg/day with regard to the final global improvement rating and other endpoints. In a noncomparative trial in patients with pruritus associated with skin diseases, the majority of bepotastine recipients in the overall population, as well as in the specific skin disease subgroups (eczema/dermatitis, prurigo or pruritus cutaneus), had a final global improvement rating of moderate or greater. Bepotastine was generally well tolerated in adult and paediatric patients with allergic conditions.

Topics: Administration, Oral; Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Hypersensitivity; Piperidines; Pruritus; Pyridines; Rhinitis, Allergic, Perennial; Urticaria

The following paper reviews the latest news on antihistamines used in the treatment of allergic rhinitis. It describes the new results of investigations on clinical application of H3 and H4 receptors in therapy of allergic diseases as well as the effect of emedastine on histamine-induced tissue remodeling. Contemporary clinical research of these drugs fulfills the requirements of placebo-controlled trials, including the comparison with a reference drug, usually cetirizine. The paper discusses efficacy and safety of a new drug--bilastine, and the possibility to improve clinical outcome by combining antihistamine drugs with inhaled glucocorticosteroids and antileukotrienes. It also presents the studies on high efficacy of nasal antihistamines, which most probably results from their high concentration in inflamed tissue, as well as describes the latest news on safe use of antihistamines, including studies of fexofenadine enantiomers in drug interactions with P-glycoprotein, safety of a new antihistamine medication--rupatadine, and psychostimulating effect of some other antihistamines. The review shows that antihistamines, the most frequently used class of anti-allergy medications, have been constantly improved, which is of significant importance for progress of allergic diseases treatment.

Topics: Administration, Inhalation; Anti-Allergic Agents; Benzimidazoles; Clinical Trials as Topic; Drug Combinations; Glucocorticoids; Histamine Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Histamine is a key mediator in the development of allergy symptoms, and oral H(1)-antihistamines are among the most widely used treatments for symptomatic relief in conditions such as allergic rhinitis and chronic urticaria. Ebastine is a second-generation antihistamine which has been shown to be an effective treatment for both seasonal and perennial allergic rhinitis. In controlled clinical trials in adult and adolescent patients with allergic rhinitis, ebastine 10 mg once-daily improved symptoms to a significantly greater extent than placebo and to a similar extent as loratadine 10 mg and cetirizine 10 mg (both once-daily), while ebastine 20 mg proved to be more effective than these two comparator antihistamines. In addition, ebastine was significantly more effective than placebo at relieving the symptoms of chronic idiopathic urticaria. Ebastine provides efficacy throughout the 24-h dosing interval with once-daily administration and clinical benefit is seen from the first day of treatment. Small studies have found beneficial effects for ebastine in patients with other disorders, including cold urticaria, dermographic urticaria, atopic asthma, mosquito bites and (in combination with pseudoephedrine) the common cold. In addition to the regular ebastine tablet, a fast-dissolving tablet (FDT) formulation, which disintegrates in the mouth without the aid of a drink, is also available. It has been shown to be bioequivalent to the regular tablet, and to be significantly more effective than desloratadine at reducing histamine-induced cutaneous wheals. A number of patient surveys demonstrated that the majority of individuals who tried the fast-dissolving formulation reported it to be convenient for use, fast-acting and preferred it to their previous antihistamine medication. Perhaps most importantly, a large proportion of patients indicated that they would prefer to use this new formulation in the future. Ebastine has a rapid onset of action and it can be administered once-daily, with or without food. Dose modifications are not needed in elderly patients, or in those with renal or mild to moderate hepatic impairment. Ebastine is generally well-tolerated, and clinical studies showed that at usual therapeutic doses of 10 and 20 mg once-daily, it had no clinically relevant adverse effects on cognitive function and psychomotor performance or on cardiovascular function. In conclusion, ebastine is an effective and generally well-tolerated treatment for allergic rhini

Topics: Animals; Butyrophenones; Chronic Disease; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Ebastine is a once-daily, non-sedating, selective, long-acting, second-generation antihistamine. The use of ebastine is indicated in patients suffering from intermittent and persistent allergic rhinitis and chronic idiopathic urticaria. Ebastine 10 mg/day, appears as effective as other second-generation antihistamines, such as cetirizine and loratadine. Ebastine 20 mg/day is indicated in patients with moderate and severe allergic symptoms. No cardiovascular effects of ebastine are described, although there is a pharmacokinetic interaction when ketoconazole or macrolides are co-administered. Ebastine has no relevant effects on the psychomotor performance. Even with ebastine 20 mg/day skilled performance does not appear to be impaired. Furthermore, ebastine 5-10 and 2.5 mg, appears to be efficient and can be used safely in children 6-11 and 2-5 years of age, respectively. Ebastine appears to be a safe, effective and well-tolerated second-generation antihistamine in the treatment of allergic rhinitis and chronic idiopathic urticaria.

Topics: Anti-Allergic Agents; Asthma; Butyrophenones; Clinical Trials as Topic; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Levocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis was inhibited by levocabastine in several allergy models. Levocabastine moderately inhibited histamine-release from guinea pig conjunctive induced by antigen-antibody reactions and prevented an increase in the vascular permeability of the conjunctive elicited by both histamine and antigen instillation. Symptoms of allergic rhinitis, which were induced by histamine, substance P and antigen, were also reduced by levocabastine. Levocabastine prevented an increase in the vascular permeability of nasal mucosa elicited by instillation of these three inducers. Furthermore, levocabastine has shown a large difference between the antiallergic dose and other non-specific pharmacological effective dose than that with other antiallergic drugs. The non-specific pharmacological effect of levocabastine reveals only blepharoptosis. With these pharmacological effects and topical usage, levocabastine was shown to be useful for allergic conjunctive and rhinitis in both seasonal and perennial clinical use.

Topics: Animals; Chemotaxis, Leukocyte; Clinical Trials as Topic; Conjunctivitis, Allergic; Depression, Chemical; Disease Models, Animal; Eosinophils; Histamine H1 Antagonists; Histamine Release; Humans; Mast Cells; Neutrophils; Piperidines; Rhinitis, Allergic, Perennial

The article presents two topical antihistaminics: levocabastine and azelastine. Most attention is paid to discussing the pharmacokinetics and antihistamine, antiallergic and antiinflammatory activities of these drugs. Their clinical usefulness in allergic rhinitis and conjunctivitis is also presented. Finally the authors describe the adverse reaction observed after administrating of topical antihistaminics.

Topics: Administration, Topical; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Cytochrome P-450 Enzyme System; Histamine H1 Antagonists; Humans; Nasal Mucosa; Phthalazines; Piperidines; Rhinitis, Allergic, Perennial

Oral antihistamines generally represent the first line of treatment (after allergen avoidance) in mild seasonal allergic rhinitis (SAR), and in perennial allergic rhinitis (PAR) where symptoms are intermittent. They are safe, effective and easily administered. First-generation antihistamines experienced problems mainly with sedation and anticholinergic activity. Second-generation antihistamines are safer and have largely eliminated these effects, although a very small number of patients taking terfenadine or astemizole have developed a characteristic ventricular dysrhythmia, 'torsade de pointes'. Ebastine is a potent second-generation H1-blocker that compares well with others in the class. It demonstrates no interaction with alcohol, does not induce sedation and has no clinically relevant effect on QTc interval at up to five times the maximum recommended dose. Ebastine acts rapidly to relieve symptoms of allergic rhinitis (including stuffiness) and has a long duration of action, allowing once-daily dosing. Whilst comparable in efficacy to other second-generation antihistamines at 10 mg, ebastine also has the advantage of flexible dosing. Thus, the lower dose of 10 mg is effective for treatment of mild SAR or PAR, and the dose can be increased to 20 mg once daily for control of patients with severe or chronic symptoms.

Topics: Butyrophenones; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sleep Stages; Torsades de Pointes

Levocabastine is a novel H1-receptor antagonist for topical use, which is being investigated in allergic rhinitis (nasal spray) and conjunctivitis (eye drops). Its anti-allergic effects have been demonstrated in nasal and ocular provocation tests. Clinical studies have been performed in 1,363 patients with allergic rhinitis and 1,218 patients with allergic conjunctivitis, comparing levocabastine mainly to placebo and cromoglycate. Levocabastine was effective when used at a dose of 2 sprays per nostril or 1 drop per eye twice daily, which if necessary can be increased up to four times daily. Levocabastine was superior to placebo in alleviating symptoms such as sneezing, itchy nose, runny nose, itchy eyes, red eyes and lacrimation. In global evaluations some 60% of patients had good to excellent results with the nasal spray and some 75% with the eye drops. Levocabastine was shown to be as good or even slightly better than cromoglycate. Onset of action was fast, with 73% of patients reporting symptom relief within 30 min after administration of levocabastine nasal spray. Adverse experiences were similar in type and incidence with levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops. The most frequent complaints were nasal and ocular irritation, respectively, with a similar incidence for the three drugs. Limited data are available in children so far, but they indicate response rate and adverse-experience profile to be similar to what was observed in adults. Levocabastine, thus, is an interesting new antihistamine available for topical use in allergic rhinoconjunctivitis. It has been extensively evaluated in adults, and preliminary data indicate that it can also be useful in allergic children.

Topics: Administration, Intranasal; Animals; Child; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Nasal Provocation Tests; Ophthalmic Solutions; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The new H1-receptor antagonist levocabastine is the most potent antihistamine available, as shown in classical animal tests for antihistamine activity. Its effects also are very specific, with doses as high as 40,000 times the effective antihistamine dose not displaying other pharmacological effects. In nasal and ocular provocation tests, levocabastine nasal spray and eye drops protected against allergen-induced nasal and ocular symptoms. Twenty-three clinical trials have been performed with levocabastine nasal spray in 1363 patients with allergic rhinitis. At a dose of two sprays per nostril twice daily (if necessary to be increased up to four times daily), levocabastine was significantly better than placebo and as good as or slightly better than cromoglycate in alleviating nasal symptoms. Good to excellent results were reported in about 60% of patients on levocabastine, compared with 37% with placebo and 47% with cromoglycate. Levocabastine eye drops were studied in 21 clinical trials including 1218 patients with allergic conjunctivitis. One drop per eye twice daily (up to four times daily) provided significantly better symptom control than placebo and similar effects as those observed with cromoglycate. Response rates were 71-80% with levocabastine, 55% with placebo and 76% with cromoglycate. Levocabastine has a fast onset of action, with 94% of patients experiencing symptom relief within 15 min after the first instillation of levocabastine eye drops. Three long-term studies (10-16 weeks' duration) showed absence of tachyphylaxis during prolonged treatment with levocabastine. The incidence of adverse experiences was similar for levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Levocabastine is a long acting, highly potent and selective histamine H1-receptor antagonist, which has been developed for nasal and ocular administration. In controlled trials performed to date levocabastine was effective and well tolerated in the treatment of allergic rhinitis and allergic conjunctivitis. Comparative studies have demonstrated that levocabastine is superior to placebo and at least as effective as sodium cromoglycate (cromolyn sodium) in alleviating symptoms associated with seasonal allergic conditions. Although levocabastine appears to be less effective than the topical corticosteroid beclomethasone with regard to relieving runny and blocked nose, further comparative trials between these 2 agents would be desirable. Similar to other antihistamines, levocabastine provides minimal relief of nasal blockage, but this symptom is believed to be mediated by receptors other than histamine H1. The prompt onset of antiallergic activity after application differentiates levocabastine from the reference topical antiallergic, sodium cromoglycate, which has an onset of efficacy characterised by a lag period, thereby necessitating maintenance treatment. The incidence of adverse effects associated with levocabastine therapy is low and is similar to that observed with placebo and sodium cromoglycate. Levocabastine provides prophylactic protection as well as acute relief from nasal and ocular symptoms in patients with seasonal allergic disorders. With the ever increasing trend towards topical therapy for the treatment of allergic rhinitis and allergic conjunctivitis, levocabastine is a useful addition to the range of drugs currently available. Possible avenues for additional research should include determining whether the antiallergic efficacy of topical levocabastine is superior to that of oral agents such as astemizole and terfenadine, and whether topical therapy is indeed preferred, considering the relative ease of administration of effective oral antiallergic agents.

Topics: Administration, Topical; Animals; Conjunctivitis, Allergic; Cromolyn Sodium; Drug Evaluation; Drug Tolerance; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial

The clinical manifestations of allergic rhinitis are the result of an immune-mediated process after exposure of a sensitized individual to airborne allergens. The primary symptomatology includes nasal congestion, rhinorrhea, nasal and conjunctival pruritus, and sneezing. Principles of management include allergen avoidance, palliative therapy, immunotherapy, and pharmacotherapy. Oral decongestants stimulate alpha-adrenergic receptors in the nasal cavity, resulting in vasoconstriction and decreased edema. Oral antihistamines block histamine1 (H1) receptors, and may relieve rhinorrhea, sneezing, and nasal and conjunctival pruritus. Topical decongestants have a local effect on adrenergic receptors in the nasal mucosa, resulting in rapid, marked vasoconstriction. Intranasal corticosteroids inhibit mediator release from mast cells and basophils, and reduce edema of the nasal mucosa. Dexamethasone sodium phosphate, beclomethasone dipropionate, and flunisolide are currently available for intranasal administration. Cromolyn sodium inhibits allergen-induced degranulation and mediator release from sensitized cells, and is useful primarily as a prophylactic agent. Several agents, including the corticosteroids budesonide and flucortin butylester, the mast cell-stabilizing agent nedocromil sodium, the anticholinergic agent ipratropium bromide, and the H1 receptor antagonist levocabastine are being investigated for intranasal use in the management of allergic rhinitis.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Glucocorticoids; Histamine H1 Antagonists; Humans; Ipratropium; Nedocromil; Piperidines; Pregnenediones; Quinolones; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR).. Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements.. Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR.. Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622).

Topics: Adult; Benzimidazoles; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Japan; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Regulations on medicinal products for paediatric use require that pharmacokinetics and safety be characterized specifically in the paediatric population. A previous study established that a 10-mg dose of bilastine in children aged 2 to <12 years provided an equivalent systemic exposure as 20 mg in adults. The current study assessed the safety and tolerability of bilastine 10 mg in children with allergic rhinoconjunctivitis and chronic urticaria.. In this phase III, multicentre, double-blind study, children were randomized to once-daily treatment with bilastine 10-mg oral dispersible table (n = 260) or placebo (n = 249) for 12 weeks. Safety evaluations included treatment-emergent adverse events (TEAEs), laboratory tests, cardiac safety (ECG recordings) and somnolence/sedation using the Pediatric Sleep Questionnaire (PSQ).. The primary hypothesis of non-inferiority between bilastine 10 mg and placebo was demonstrated on the basis of a near-equivalent proportion of children in each treatment arm without TEAEs during 12 weeks' treatment (31.5 vs. 32.5%). No clinically relevant differences between bilastine 10 mg and placebo were observed from baseline to study end for TEAEs or related TEAEs, ECG parameters and PSQ scores. The majority of TEAEs were mild or moderate in intensity. TEAEs led to discontinuation of two patients treated with bilastine 10 mg and one patient treated with placebo.. Bilastine 10 mg had a safety and tolerability profile similar to that of placebo in children aged 2 to <12 years with allergic rhinoconjunctivitis or chronic urticaria.

Topics: Adolescent; Adult; Benzimidazoles; Child; Child, Preschool; Chronic Disease; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Treatment Outcome; Urticaria

Although second-generation antihistamines, such as bepotastine besilate, are recommended as a first-line treatment option for adult perennial allergic rhinitis (PAR), few non-sedating second-generation antihistamines are safe for children.. A double-blind, placebo-controlled, comparative study of 473 pediatric PAR patients (7 - 15 years old) to determine the superiority and safety of bepotastine besilate (10 mg twice daily) relative to placebo for improved total and individual nasal symptom scores compared with baseline.. Subjects were randomized to placebo (n = 233) or bepotastine besilate (n = 240, 10 mg orally twice daily for 2 weeks). Interference of daily life by PAR was assessed by measuring change in individual nasal symptom scores from baseline.. Bepotastine besilate was superior to placebo in terms of total nasal symptom scores, with improved overall nasal symptoms of PAR compared with baseline values. Subgroup analyses demonstrated bepotastine besilate was effective irrespective of age, sex or body weight. No clinically significant adverse drug reactions often observed with first-generation antihistamines were reported and no difference in adverse events between groups was observed.. Bepotastine besilate is effective and safe for pediatric PAR patients aged 7 - 15 years, and has a significant clinical impact on PAR.. ClinicalTrials.gov identifier: NCT01861522 ( https://clinicaltrials.gov/ct2/show/NCT01861522 ).

Topics: Adolescent; Child; Double-Blind Method; Histamine Antagonists; Humans; Piperidines; Pyridines; Rhinitis, Allergic, Perennial

Bilastine is a non-sedating second-generation H(1) antihistamine with proven efficacy and safety in the treatment of patients with seasonal allergic rhinitis and urticaria. The objective of this study was to demonstrate the efficacy and safety of bilastine in patients with perennial allergic rhinitis (PAR).. In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients with symptomatic PAR (n = 650) from Argentina, Europe, and South Africa received bilastine 20 mg, cetirizine 10 mg, or placebo once daily for 4 weeks. The primary efficacy outcome was the mean area under the curve (AUC) of reflective total 6-symptom scores (rT6SS) from baseline visit to day 28 (D28). Secondary outcome measures included mean AUC of instantaneous total 6-symptom scores (iT6SS), and mean AUCs of reflective and instantaneous total 4-nasal symptom scores (T4NSS) and total 2-ocular symptom scores (T2OSS) from baseline to D28. An open-label extension phase evaluated the safety of bilastine 20 mg administered to patients (n = 513) for one year.. In the overall population no significant differences in efficacy outcomes were found between active treatments and placebo. On account of the high placebo response in South Africa, a post-hoc analysis was conducted. This analysis demonstrated that statistically significant differences existed between active treatments and placebo in the mean AUC of rT6SS (p < 0.05) and T4NSS (p < 0.02), respectively, from baseline to D28 visit for the intent-to-treat population in patients from Europe and Argentina, whereas the difference was not statistically significant in South Africa. Whether this is related to differences in the demographic or clinical characteristics of South African patients (they had PAR for longer and reported more severe symptoms) and/or the disease management process compared with their European and Argentinean counterparts warrants further investigation.. A post-hoc analysis indicated that bilastine and cetirizine were similarly effective and more effective than placebo during a 4-week treatment period in patients with PAR. In addition, bilastine was shown to be safe and well-tolerated over a 1-year treatment period.. NCT01127620.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Argentina; Benzimidazoles; Cetirizine; Child; Dosage Forms; Double-Blind Method; Drug Administration Schedule; Europe; Female; Humans; Male; Middle Aged; Piperidines; Placebos; Rhinitis, Allergic, Perennial; South Africa; Treatment Outcome; Young Adult

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.

Topics: Administration, Intranasal; Adolescent; Adult; Diuretics; Female; Furosemide; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Perennial; Rhinomanometry; Saline Solution, Hypertonic; Time Factors; Young Adult

Azelastine is a selective H(1)-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC). The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo.. A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment.. Azelastine significantly improved itching and conjunctival redness compared to placebo (p < 0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9 +/- 1.1 and with levocabastine by 1.5 +/- 1.2 compared to placebo (0.6 +/- 1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction.. Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H(1)-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.

Topics: Administration, Topical; Adolescent; Adult; Aged; Analysis of Variance; Anti-Allergic Agents; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Phthalazines; Piperidines; Rhinitis, Allergic, Perennial

This double-blind, placebo-controlled, multicentre study investigated the ability of ebastine, 10 and 20 mg once daily, to control symptoms of perennial allergic rhinitis (PAR) over a 12-week period, and assessed additional benefits of the 20-mg dose. Following a 2-week baseline period, patients (12-63 years) were randomized to treatment with ebastine 10 mg (n=88) or 20 mg (n=102), or placebo (n=100). Patients scored symptom severity (0-3) twice daily, and mean changes from baseline scores showed ebastine to be significantly effective in week 1. Control of symptoms persisted over the 12 weeks, the average daily total nasal symptom score for nasal stuffiness plus nasal discharge plus sneezing plus itchy nose being reduced by both doses, with statistical significance at 20 mg (P=0.015 vs placebo) despite decreased usage of sodium cromoglycate rescue medications. Patient and clinician final opinions of treatment also significantly favoured ebastine, both 10 and 20 mg, over placebo. No serious adverse events occurred, and study treatments were well tolerated with a low incidence of central nervous system-related adverse events and headache. In conclusion, ebastine 10 or 20 mg once daily was rapidly effective in relieving symptoms of PAR in adult and adolescent patients; additional benefits of the 20-mg dose became apparent in the longer term.

Topics: Adolescent; Adult; Butyrophenones; Child; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Treatment Outcome

Ebastine is a nonsedating and selective histamine H1 receptor antagonist without anticholinergic or sedative effects at therapeutic doses. It has shown a rapid onset and long duration of action, and doses of 10 and 20mg once daily are effective in relieving the nasal and non-nasal symptoms of seasonal and perennial allergic rhinitis (SAR and PAR, respectively). In 3 randomised double-blind, multicentre clinical trials in patients with SAR, ebastine 10 and 20mg once daily for 2 to 3 weeks significantly reduced symptoms (nasal discharge, stuffiness, sneezing, itchy nose, itchy/watery eyes) when compared with placebo. Similarly, in patients with PAR, two 3-week studies demonstrated that ebastine 10mg twice daily and 20mg once daily significantly relieved the symptoms of PAR, as measured by the Perennial Index. Ebastine was well tolerated in these studies and had no effect on the QTc interval.

Topics: Adolescent; Adult; Aged; Butyrophenones; Child; Double-Blind Method; Electrocardiography; Electrocardiography, Ambulatory; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Cetirizine and ebastine are two second-generation histamine H1 antagonists undergoing evaluation for treatment of perennial rhinitis.. The clinical efficacy and safety of once daily cetirizine 10 mg were compared with ebastine 10 mg in patients with perennial allergic rhinitis in a 4-week, double-blind, parallel-group, randomized, multicenter study.. Two hundred fourteen patients (120 females, 94 males, aged 17 to 70 years, mean 31.2 years) were selected on the basis of perennial allergic rhinitis history, positive skin test for perennial allergens and a minimum rhinitis symptom score of 6/12. Patients recorded nasal symptom severity (nasal stuffiness, nasal discharge, sneezing, and itching) once daily on diary cards using a rating scale of 0 (none) to 3 (severe). Clinicians made an overall evaluation after 4 weeks of treatment. An intent-to-treat-analysis was performed comparing cetirizine (106 patients) and ebastine groups (108 patients).. The individual and total baseline symptom scores were comparable in both treatment groups. During the first week, the percentage mean decrease in the total nasal symptom score from baseline (sum of nasal stuffiness, discharge, sneezing, and itching) was significantly higher for cetirizine 46.2% than for ebastine 32.8% (P = .037). After 4 weeks of treatment, total symptom score improvement was 53.7% for cetirizine and 44.7% for ebastine (P = .12), and the clinician's overall evaluation showed that the percentage of symptom-free patients was significantly higher for cetirizine 17.8% than for ebastine 6.9% (P = .02). Cetirizine also significantly improved nasal stuffiness. An associated antiinflammatory effect is suggested. Commonly reported drug-related side effects were similar in both groups.. This study shows that both antihistamines, cetirizine 10 mg and ebastine 10 mg once a day, improved symptom scores of patients with perennial allergic rhinitis. Cetirizine, however, provided faster improvement and total relief in a greater number of patients after 4 weeks.

Topics: Adolescent; Adult; Aged; Butyrophenones; Cetirizine; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial

It has been hypothesized that concentrations of exhaled nitric oxide (NO) may be related to the extent of cytokine-mediated airway inflammation. Recent findings indicate the nasal airways as an important site of NO production. Our objective was to evaluate whether children with allergic rhinitis show different nasal NO levels when compared with normal healthy subjects and the effect of topical steroids and anti-histamine therapy. We have measured the concentration of NO drawn from the nose of 21 children (5-17 years old) affected by perennial allergic rhinitis (house dust mite) out of therapy for at least 3 weeks. Thirteen children were then treated with nasal beclomethasone dipropionate (BDP) (400 micrograms daily) and eight subjects with nasal anti-histamine levocabastine (200 micrograms daily). Measurements were performed before and after 10 days of treatment. As a control group we evaluated 21 healthy children aged 5-15 years. To measure NO we used a chemiluminescence analyser. Before treatment the whole group of children with allergic rhinitis showed a mean (+/- SEM) nasal NO concentration of 267 +/- 18 ppb, significantly higher (P < 0.01) than the control group (186 +/- 15 ppb). The group of children treated with BDP showed, after 10 days of therapy, a significant (P < 0.05) decrease of nasal NO concentration (271 +/- 21 ppb vs. 212 +/- 20 ppb). Indeed, in the group treated with levocabastine, nasal NO concentrations did not present a significant difference (P not significant) compared with baseline (261 +/- 33 ppb and 252 +/- 31 ppb, respectively). These data suggest that (1) children with allergic rhinitis have higher levels of nasal NO than non-atopic controls and (2) intranasal steroid therapy significantly reduces nasal NO production in children with allergic rhinitis. We speculate that the allergic inflammatory response may influence the nasal NO levels and that NO measurements may be a useful marker of nasal inflammation.

Topics: Adolescent; Anti-Inflammatory Agents; Beclomethasone; Child; Child, Preschool; Female; Histamine H1 Antagonists; Humans; Male; Nitric Oxide; Pilot Projects; Piperidines; Rhinitis, Allergic, Perennial; Treatment Outcome

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean=125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis.

Topics: Allergens; Budesonide; Cell Line; Chemotactic Factors; Chemotaxis, Leukocyte; Enzyme-Linked Immunosorbent Assay; Humans; Mast Cells; Nasal Lavage Fluid; Nasal Provocation Tests; Piperidines; Pollen; Rhinitis, Allergic, Perennial; Single-Blind Method; Stem Cell Factor

The ultrastructure of the nasal mucosa following the use of intranasal levocabastine was studied in 20 patients suffering from perennial allergic rhinitis. The patients received twice daily 0.05 per cent levocabastine spray with a treatment duration of four weeks. At the end of the treatment period regression of the allergic process was evidenced by progressive reappearance of normal cilia and microvilli on the columnar cells, decrease of intercellular oedema and cytoplasmic vacuoles, increased number of mucous acinar cells, gradual decrease of vascular congestion, as well as diminished oedema fluid formation. The drug, however, had no effect on mast cell degranulation nor on eosinophilic infiltration. Normalization of the ultrastructural features correlated well with clinical improvement. Considering the results of the present study, levocabastine nasal spray appears to be an effective treatment for perennial allergic rhinitis and can be used with, or as an alternative to, other anti-allergic medications.

Topics: Administration, Intranasal; Adult; Chronic Disease; Female; Histamine H1 Antagonists; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Nasal Mucosa; Piperidines; Rhinitis, Allergic, Perennial; Treatment Outcome

We have evaluated the efficacy of topical levocabastine in 42 patients (20 males and 22 females; mean age 37.5 yrs.) affected by perennial allergic rhinoconjunctivitis due to Dermatophagoides pteronyssinus. Diagnosis was performed on the basis of clinical history, Skin Prick test and RAST. The study lasted for 90 days and nasal spray levocabastine was administered at the dose of 2 puff in each nostril twice a day. Patients had to record the severity of the symptoms considered (sneezing, nasal pruritus, nasal obstruction and rhinorrhea) on a diary card according to an arbitrary score from 0 to 3. At the end of the treatment patients experienced a significant improvement of their symptoms and no side effects were recorded. On the basis of our results levocabastine can be considered a useful drug in the treatment of allergic rhinitis due to Dermatophagoides pteronyssinus.

Topics: Administration, Intranasal; Adult; Aerosols; Analysis of Variance; Conjunctivitis; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial

Ebastine is H1 receptor antagonist, powerful and selective for histamine. Its efficacy has been evaluated in control of symptoms of persistent rhinitis, appearance of secondary effects and tolerance of the drug, in 30 children who were suffering from persistent rhinitis, of which the diagnosis included:- clinical history, skin tests (prick test) nasal and conjunctival provocation tests, total and specific IgE. All the children had treatment for 30 days. The parameters followed were:- clinical score, skin tests, nasal and conjunctival provocations and evaluation of secondary effects, of the start and 10 days after the end of treatment. The results obtained were a disappearance or reduction of the weals from histamine and specific antigens, disappearance or reduction of the response in nasal and conjunctival provocation with carbachol or specific antigens, clear clinical improvement in 22 patients, in 2 small improvement and no response in 6 patients. We conclude that Ebastine improved the clinical symptoms in persistent rhinitis, the skin test is inhibited and sensitivity of the shock organ is reduced. No secondary effects were seen on the Central Nervous System (SNC) and the tolerance of the drug was very good.

Topics: Adolescent; Butyrophenones; Carbachol; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists; Humans; Male; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Perennial; Skin Tests; Treatment Outcome

It has been demonstrated that some oral antihistamines reduce nasal nonspecific reactivity and that topical levocabastine reduces cellular influx after nasal allergen challenge. This suggests that antihistamines possess other properties besides classical H1-receptor antagonism.. To evaluate the effect of 1 week's treatment with topical levocabastine on the nasal clinical response, inflammatory mediators, and nasal hyperreactivity.. In a double-blind, placebo-controlled, 2-period, 2-treatment, crossover study, 21 rhinitic patients allergic to house dust mite participated. After each treatment period patients were challenged with house dust mite extract. Symptom scores and nasal lavages were collected for nine and one-half hours after challenge. Allergen-induced nasal hyperreactivity was determined by nasal methacholine challenge 24 hours after allergen challenge. A nasal histamine challenge was performed as well.. Patients showed only an immediate nasal response. Levocabastine significantly reduced the symptom score after 100 (P = .0063), 1000 (P = .0035), and 10,000 biological units (BU)/mL (P = .0013) of house dust mite extract. Albumin influx and tryptase release were not significantly reduced by levocabastine. No release of histamine and eosinophil cationic protein was seen. Levocabastine did not reduce nasal response to methacholine. Active treatment significantly reduced histamine-induced nasal secretion (P = .0009) and the number of sneezes (P = .0001).. A significant effect of levocabastine was shown on the immediate clinical response to house dust mite and to histamine challenge only. Our findings suggest that levocabastine is an effective H1-receptor antagonist without anti-inflammatory properties.

Topics: Administration, Topical; Adult; Albumins; Allergens; Animals; Antigens, Dermatophagoides; Chymases; Cross-Over Studies; Double-Blind Method; Female; Glycoproteins; Histamine; Histamine H1 Antagonists; Humans; Male; Methacholine Chloride; Middle Aged; Mites; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Perennial; Serine Endopeptidases; Tryptases

For evaluation of the effect of levocabastine pretreatment on allergen-induced rhinitis symptoms, changes in nasal washings, and nasal responsiveness to histamine, 12 asymptomatic patients with documented allergic rhinitis participated in a single-blind, placebo-controlled study. Eight-day treatment with levocabastine (twice in each nostril, four times a day) caused significant reduction in nasal symptoms and inflammatory cell influx after allergen challenge, as compared with placebo administration. Levocabastine inhibited increased nasal reactivity to histamine induced by allergen provocation, as controlled by rhinitis symptoms and albumin level in nasal washings. These data reveal a high effectiveness of levocabastine in the prevention of allergen-induced rhinitis symptoms. Moreover, its inhibitory effect on inflammatory cell influx and hyperresponsiveness to histamine suggest that levocabastine is more than a simple H1-receptor antagonist.

Topics: Adult; Albumins; Allergens; Animals; Cell Count; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Mites; Nasal Lavage Fluid; Nasal Provocation Tests; Piperidines; Rhinitis, Allergic, Perennial

Ebastine is a new piperidine-containing, relatively nonsedating second-generation H1-receptor antagonist. In a double-blind, parallel-group study of a single 5 mg or 10 mg dose of ebastine syrup used to treat allergic rhinitis in 20 children aged 6 to 12 years, we tested the hypothesis that the medication would have a duration of action of at least 24 hours. We measured plasma concentrations of carebastine, the pharmacologically active metabolite of ebastine, and the wheals and flares produced by epicutaneous tests with histamine phosphate, 1.0 mg/ml. Ebastine was absorbed well; peak carebastine concentrations occurred approximately 3 hours after dosing. Mean plasma elimination half-life values of carebastine ranged from 10 to 14 hours. The pharmacokinetics of carebastine were linear and dose independent in the dosage range studied. After the 5 or 10 mg dose, there were no significant differences between mean plasma elimination half-life values, mean oral clearance values, or mean apparent volumes of distribution. Mean peak plasma carebastine concentrations and mean areas under the plasma carebastine concentration-time curve after the 10 mg dose were 1.93 and 1.76 times, respectively, the values obtained after the 5 mg dose. Both doses significantly reduced the histamine-induced wheal-and-flare areas for up to 28 hours compared with predose values. The differences in effect between the doses generally were not statistically or clinically significant. No adverse effects were noted. We conclude that ebastine, an effective H1-receptor antagonist with a prompt onset of action and a long duration of action, is suitable for once-daily administration to children.

Topics: Butyrophenones; Child; Double-Blind Method; Drug Administration Schedule; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Skin Tests

Oral ebastine, 10 mg once daily for seven days, and placebo were compared as treatment for active perennial allergic rhinitis in 151 patients in a multicenter, randomized, double-blind trial. Ebastine treatment produced a significant reduction in the incidence and severity of most symptoms associated with perennial rhinitis. Tolerability was similar in the two treatment groups. The incidences of drowsiness and dry mouth were not more frequent in the patients treated with the active drug.

Topics: Adult; Butyrophenones; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Time Factors

Forty-four patients, with symptoms of nasal obstruction, sneezing, itching and/or rhinorrhea, were entered into a placebo-controlled, double-blind study to evaluate the clinical efficacy of a topical antihistamine drug, levocabastine, applied 4 times a day for 14 days. At the end of the treatment the placebo patients were treated with levocabastine and the levocabastine patients were treated with beclomethasone dipropionate in a single-blind design for another 14 days. This study showed that levocabastine is significantly more active than placebo with reference to nasal discharge and sneezing. Placebo application improved the symptom score. Levocabastine could not be proved to be more effective against nasal obstruction than placebo in the double-blind trial. In the single-blind set-up, levocabastine resulted in an additional improvement in the score for obstruction, after the placebo period. Although the allergic group tended to respond better, no statistically significant difference could be detected between allergic and non-allergic patients. After treatment with levocabastine, beclomethasone dipropionate administration could not improve the results for nasal discharge and sneezing. For nasal congestion, beclomethasone dipropionate proved to be superior to levocabastine.

Topics: Administration, Intranasal; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Bepotastine besilate (BB) is a second-generation H1-antihistamine that, as an ophthalmic solution, is approved in the United States by the Food and Drug Administration (FDA) for the treatment of allergic conjunctivitis. In other countries, the oral presentation of BB is widely used for the improvement of symptoms of allergic rhinitis (AR) as well as urticaria and chronic pruritus with results similar to those by other drugs of the same class. Areas covered: This article was created from a comprehensive literature search with information taken from clinical trials. The articles that have been selected evaluate the clinical and non-clinical pharmacology of BB as well as its use in AR and its efficiency in the improvement of symptoms, its safety, common adverse effects, and overall experiences of its use. Expert opinion: BB is effective and well-tolerated in the treatment of allergic rhinitis. Side effects are infrequent in patients with AR who do not have kidney or liver disease. Clinical trial experience with oral bepotastine outside the United States has confirmed its safety. BB can be useful as a therapeutic option in patients with AR who would like to explore an alternative to the currently available once-daily oral H1-antihistamines.

Topics: Humans; Piperidines; Pyridines; Rhinitis, Allergic, Perennial

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

Topics: Administration, Oral; Benzimidazoles; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

We report the anesthetic management of a narcoleptic patient performed using sevoflurane-remifentanil with bispectral index (BIS) monitoring. A 22-year-old man, who was diagnosed with narcolepsy at the age of 17, requested endoscopic sinus surgery, under general anesthesia, for chronic allergic rhinitis. On the morning of the day of operation, he took his daily dose of modafinil, used to control narcolepsy. Anesthesia was induced by 5% sevoflurane and maintained with sevoflurane and continuous infusion of remifentanil and 60% oxygen in conjunction with BIS monitoring. BIS values were between 47 and 58. Duration of surgery was 150 min. After surgery, the patient emerged from anesthesia within 10 min and was extubated. His recovery was uneventful. We found the use of BIS monitoring for titrating sevoflurane concentration in a narcoleptic patient is useful for preventing not only oversedation but also intraoperative awareness caused by the preoperative medication.

Topics: Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Anti-Inflammatory Agents, Non-Steroidal; Benzhydryl Compounds; Central Nervous System Stimulants; Consciousness Monitors; Endoscopy; Flurbiprofen; Humans; Hypnotics and Sedatives; Male; Methyl Ethers; Modafinil; Narcolepsy; Pain, Postoperative; Piperidines; Remifentanil; Rhinitis, Allergic, Perennial; Sevoflurane; Sinusitis; Young Adult

Preclinical pharmacological characterization of GSK1004723, a novel, dual histamine H(1) and H(3) receptor antagonist.. GSK1004723 was characterized in vitro and in vivo using methods that included radioligand binding, intracellular calcium mobilization, cAMP production, GTPγS binding, superfused human bronchus and guinea pig whole body plethysmography.. In cell membranes over-expressing human recombinant H(1) and H(3) receptors, GSK1004723 displayed high affinity, competitive binding (H(1) pKi = 10.2; H(3) pKi = 10.6). In addition, GSK1004723 demonstrated slow dissociation from both receptors with a t(1/2) of 1.2 and 1.5 h for H(1) and H(3) respectively. GSK1004723 specifically antagonized H(1) receptor mediated increases in intracellular calcium and H(3) receptor mediated increases in GTPγS binding. The antagonism exerted was retained after cell washing, consistent with slow dissociation from H(1) and H(3) receptors. Duration of action was further evaluated using superfused human bronchus preparations. GSK1004723 (100 nmol·L(-1) ) reversed an established contractile response to histamine. When GSK1004723 was removed from the perfusate, only 20% recovery of the histamine response was observed over 10 h. Moreover, 21 h post-exposure to GSK1004723 there remained almost complete antagonism of responses to histamine. In vivo pharmacology was studied in conscious guinea pigs in which nasal congestion induced by intranasal histamine was measured indirectly (plethysmography). GSK1004723 (0.1 and 1 mg·mL(-1) intranasal) antagonized the histamine-induced response with a duration of up to 72 h.. GSK1004723 is a potent and selective histamine H(1) and H(3) receptor antagonist with a long duration of action and represents a potential novel therapy for allergic rhinitis.

Topics: Allergens; Animals; Benzazepines; Binding, Competitive; Bronchi; Bronchial Provocation Tests; Bronchoconstriction; Carbachol; Cell Line; CHO Cells; Cricetinae; Cricetulus; Female; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine H3 Antagonists; Humans; In Vitro Techniques; Niacinamide; Ovalbumin; Phthalazines; Piperidines; Pyrilamine; Receptors, Histamine H1; Receptors, Histamine H3; Recombinant Proteins; Rhinitis, Allergic, Perennial; Transfection

Topics: Benzimidazoles; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

To investigate the expression and distribution of aquaporin 5 (AQP5) in allergic rhinitis (AR) treated by fluticasone propionate and levocabastine.. Forty Wistar rats were divided randomly into AR (n=30) and control groups (n=10). After AR models were established, the AR rats were divided evenly into F group, L group and AR control group. Three groups were treated respectively for 28 days, then the expression of AQP5 in nasal mucous membrane were detected by immunohistochemistry assay.. The distribution of AQP5 was consistent in all groups. The expression of AQP5 in F group was significantly different from L group and AR group (P<0.05), while there was no significant difference between that of AR group and L group (P>0.05). The expression of AQP5 in L group was significantly different from that in control group (P<0.05).. High expressions of AQP5 in rat with AR indicated the positive correlation between AQP5 and AR. AQP5 might be one of pathological factors of AR concerned with glands excessive secretion and tissue edema. Glucocorticoid can down-regulate the expression of AQP5, but H1-receptor antagonist can not reduce the expression of AQP5.

Topics: Androstadienes; Animals; Aquaporin 5; Fluticasone; Nasal Mucosa; Piperidines; Rats; Rats, Wistar; Rhinitis, Allergic, Perennial

The aim of this study was to clarify the mechanisms of the inhibitory effect of a histamine H3 receptor agonist, Sch 50971, on nasal signs in an allergic rhinitis model in mice. The severity of allergic rhinitis was assessed by determining the extent of two markers of allergic symptoms (sneezing and nasal rubbing). The topical application of a histamine H3 receptor antagonist, clobenpropit, into the nasal cavities resulted in a dose-dependent increase in sneezing and nasal rubbing, and both Sch 50971 and a tachykinin NK1 receptor antagonist, L-733,060, inhibited these reactions in non-sensitized mice. Sch 50971 caused no inhibition of histamine- and substance P-induced nasal symptoms; however, the reactions induced by capsaicin were significantly decreased by Sch 50971 in non-sensitized mice. Sch 50971 and cetirizine inhibited antigen-induced sneezing and nasal rubbing in sensitized mice. On the other hand, cetirizine inhibited nasal symptoms induced by antigen in capsaicin-pretreated mice, whereas no effect was observed in Sch 50971. From these results, we concluded that Sch 50971 blocked nasal symptoms by the inhibition of substance P release via histamine H3 receptors located on peri]pheral sensory nerve endings.

Topics: Animals; Capsaicin; Cetirizine; Disease Models, Animal; Female; Histamine; Histamine Agonists; Histamine H1 Antagonists, Non-Sedating; Imidazoles; Mice; Mice, Inbred BALB C; Ovalbumin; Piperidines; Pyrrolidines; Receptors, Histamine H3; Rhinitis, Allergic, Perennial; Substance P; Thiourea

Histamine is an important chemical mediator of allergic rhinitis (AR). Histamine H(3) receptors (H(3)R) are located on cholinergic and NANC neurons of the myenteric plexus, and activation of H(3)R regulates gastric acid secretion. However, little is known about the localization and function of H(3)R in the upper airway.. The objective of this study was to examine the localization and possible function of H(3)R in the nasal mucosa.. We extracted total RNA from the inferior turbinate mucosa of patients with AR. H(3)R mRNA and beta-actin mRNA were amplified by RT-PCR. We used immunohistochemistry to examine localization of H(3)R protein in the inferior turbinate mucosa excised during clinically indicated surgery. We used alcian blue/periodic acid-shiff staining to examine the effects of the H(3)R agonist (R)-alpha-methylhistamine and the H(3)R antagonist thioperamide on secretion from rat submucosal glands.. H(3)R protein was expressed around submucosal gland cells. Thioperamide induced degranulation in the submucosal gland in the nasal septum.. The present results suggest that H(3)R is localized mainly around submucosal glands, and that H(3)R plays an important role in the secretion of submucosal glands in the nose.

Topics: Adolescent; Adult; Animals; Histamine H3 Antagonists; Humans; Immunohistochemistry; Male; Methylhistamines; Middle Aged; Nasal Mucosa; Piperidines; Rats; Rats, Inbred F344; Receptors, Histamine H3; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic, Perennial; RNA, Messenger; Young Adult

Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Butyrophenones; Cetirizine; Child; Chlorpheniramine; Dermatitis, Atopic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Imidazoles; Japan; Male; Middle Aged; Olopatadine Hydrochloride; Pain Measurement; Piperidines; Population Surveillance; Psychomotor Performance; Pyridines; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sleep Stages; Surveys and Questionnaires; Terfenadine; Urticaria

CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy.. HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA.. The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups.. This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Butyrophenones; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines, CC; Child; Dibenzoxepins; Dose-Response Relationship, Drug; Epithelial Cells; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Mucosa; Olopatadine Hydrochloride; Piperidines; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Adult; Butyrophenones; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial

Topics: Anti-Allergic Agents; Butyrophenones; Cetirizine; Double-Blind Method; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Multicenter Studies as Topic; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Time Factors

Topics: Anti-Allergic Agents; Benzimidazoles; Butyrophenones; Cetirizine; Double-Blind Method; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Meta-Analysis as Topic; Piperidines; Placebos; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

To observe the effect of Livostin spray on children's allergic rhinitis and to search the mechanism of treating allergic rhinitis.. 113 patients were treated with Livostin spray (Livostin group) or normal saline spray (control group).. The total efficiency of Livostin group in treating allergic rhinitis is above 95.1% and that of the control group is 25.0%. Initial time of starting effect of Livostin (72.1%) is in 1 minute, and that of the control group (mostly 23.1%) is in 3 minutes. The keeping curative effect time of Livostin spray is mostly (72.1%) above 5 hours and that of the control group is mostly (30.8%) in 3 hours. After 2 weeks, the eosinophilic granulocyte number in nose's secretion of Livostin group is obviously reduced (P < 0.05).. Livostin is better than control group in relieving symptoms, keeping curative effect and safety, so Livostin is one kind of effective drug in treating children's allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Aerosols; Child; Child, Preschool; Female; Histamine H1 Antagonists; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial

We investigated the effect of betotastine besilate (betotastine) on the experimental allergic rhinitis. The oral administration of betotastine (1, 3 and 10 mg/kg) inhibited the increase in dye leakage during and after the nasal perfusion of antigen in actively sensitized rats. It also prevented the increase in intranasal pressure induced by topically applied histamine in non-sensitized guinea pigs. Cetirizine and terfenadine dose-dependently inhibited the increase in a similar manner. Ketotifen (0.01-0.3 mg/kg, p.o.) inhibited the increase more than 50% at 0.01 mg/kg. The ID50s of ketotifen, cetirizine, betotastine and terfenadine for this model were more than 0.01 mg/kg, 0.01 mg/kg, 0.03 mg/kg and 0.5 mg/kg, respectively. Furthermore, in actively sensitized guinea pigs, nasal airway resistance showed a biphasic increase after the topical antigen challenge to the nasal cavity; the first peak at 0.5 hr and a second peak at 4 hr. Both the responses of first and second peaks were significantly inhibited by orally administered betotastine besilate, and its inhibitory effect on the second peak was the strongest among drugs tested. Since betotastine showed significantly inhibitory effects in experimental allergic rhinitis models, it was suggested to show a good efficacy for the treatment of allergic rhinitis clinically.

Topics: Airway Resistance; Animals; Anti-Allergic Agents; Capillary Permeability; Disease Models, Animal; Guinea Pigs; Humans; Infant; Male; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic, Perennial

Topics: Anti-Allergic Agents; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Nedocromil; Piperidines; Rhinitis, Allergic, Perennial

Topics: Benzhydryl Compounds; Chemical Phenomena; Chemistry; Child; Child, Preschool; Female; Humans; Male; Piperidines; Rhinitis, Allergic, Perennial; Terfenadine

Topics: Adolescent; Adult; Clemastine; Cromolyn Sodium; Female; Humans; Ketotifen; Male; Middle Aged; Piperidines; Rhinitis, Allergic, Perennial; Thiophenes