olopatadine-hydrochloride and epinastine

To address the current trends of therapeutic mechanisms for treatment of allergic conjunctivitis (AC), based on topical antihistamines and mast cell stabilizers (MCS).. The antihistamine drug alcaftadine has H4 receptor inverse agonism, anti-inflammatory and MCS activities. The antihistamines levocabastine and azelastine are more effective than placebo in treatment of AC symptoms in randomized controlled trials (RCTs). The topical dual-action antihistamines/MCS olopatadine, azelastine, ketotifen, and epinastine are commonly used in Europe and in the United States for mild subtypes of AC. For the main symptoms of AC, ocular itch and conjunctival hyperemia, epinastine 0.05% was superior to placebo, but equal or more effective than olopatadine 0.1%, while the later was more effective than ketotifen. High concentration olopatadine 0.77% had longer duration of action, better efficacy on ocular itch, and a similar safety profile to low-concentration olopatadine 0.2%. The new formulas of topical dual-action agents present longer duration of action, leading to a decreased frequency of use.. The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Cromolyn Sodium; Dibenzazepines; Histamine Antagonists; Humans; Hyperemia; Imidazoles; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Phthalazines; Piperidines; Pruritus; Pyridines; Pyrimidinones

To assess the safety and efficacy of topical olopatadine versus placebo and other topical anti-allergic medications in treating allergic conjunctivitis.. We systematically searched the literature for randomized-controlled trials that included patients with allergic conjunctivitis, compared olopatadine versus placebo or alternative anti-allergic medications, and examined itch, conjunctival hyperemia, composite symptom or sign scores, and/or occurrence of adverse events. We assessed the safety and efficacy of topical olopatadine when compared with placebo or alternative anti-allergic medications using meta-analysis.. When compared with placebo, topical olopatadine is associated with a pooled-mean difference (MD) in ocular itch of -1.33 (p < 0.00001) and ocular hyperemia of -0.92 (p < 0.00001). When compared with other agents, olopatadine was inferior to alcaftadine on ocular itch (pooled-MD = 0.39; p < 0.00001) but comparable with epinastine and ketotifen.. Topical olopatadine is a safe and effective treatment modality for allergic conjunctivitis, whereas alcaftadine appears to be superior to olopatadine in reducing ocular itch.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Dibenzazepines; Histamine H1 Antagonists; Humans; Imidazoles; Ketotifen; Olopatadine Hydrochloride; Ophthalmic Solutions; Treatment Outcome

Multiple action drugs, such as azelastine, epinastine, ketotifen and olopatadine, have recently been suggested to combine antihistaminic effect, mast cell stabilization and anti-inflammatory action. This pharmaceutical class is, therefore, rapidly becoming the first choice for prevention and treatment for allergic conjunctivitis.. Increasing in-vitro studies have been performed to investigate the mast-cell-stabilizing effect of multiple action drugs. Most of the study results agree that these drugs are able to inhibit histamine and several neoformed mediators, including cytokines and arachidonic acid-derived products, from mast cells. However, the mechanisms of action have not yet fully been elucidated. Most of the results from clinical trials as well as the in-vivo experimental studies, including the conjunctival provocation model, support the evidence of a stabilizing effect of these drugs.. Evidence of a different inhibitory effect of multiple action compounds on the pro-inflammatory mediators released from the mast cells suggests the possibility to target different phases of the allergic reaction, leading to a potential improvement in the management of allergic patients.

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acid; Conjunctivitis, Allergic; Cytokines; Dibenzazepines; Dibenzoxepins; Histamine; Histamine Antagonists; Humans; Imidazoles; Immunity, Innate; Ketotifen; Mast Cells; Olopatadine Hydrochloride; Phthalazines

Epinastine hydrochloride is a selective histamine H1 receptor antagonist that also inhibits IgE receptor-mediated histamine release from mast cells.. To show the superiority of epinastine 0.05% ophthalmic solution (epinastine) to placebo ophthalmic solution (placebo) and noninferiority to olopatadine 0.1% ophthalmic solution (olopatadine) for cedar pollen antigen-induced ocular itching and conjunctival hyperemia.. The study was conducted in ophthalmologically asymptomatic adult volunteers with seasonal allergic conjunctivitis using a conjunctival allergen challenge test. Subjects were randomized into 3 groups (n = 87) to evaluate superiority to placebo (visits 4 to 6) and 2 groups (n = 86) to evaluate noninferiority to olopatadine (visit 7). At each visit, a single administration of the study medication was instilled at 15 minutes (visit 4), 4 hours (visit 5), 8 hours (visit 6), and 4 hours (visit 7) before the conjunctival allergen challenge test. Ocular itching and conjunctival hyperemia of allergic conjunctivitis were assessed after the conjunctival allergen challenge test.. For the primary end point, epinastine showed superiority to placebo for the inhibition of ocular itching and conjunctival hyperemia induced at 4 hours after the dose (equivalent to 4-times-daily dosing). For the secondary end points, epinastine significantly inhibited itching and conjunctival hyperemia induced at 15 minutes and 8 hours after the dose (equivalent to 2-times-daily dosing) compared with placebo. In addition, epinastine demonstrated noninferiority to olopatadine for ocular itching and conjunctival hyperemia. No adverse drug reactions or serious adverse events were reported throughout the study, indicating that epinastine has a good safety profile.. Epinastine is effective and safe for the treatment of allergic conjunctivitis.. Clinicaltrials.gov identifier NCT01363700.

Topics: Adult; Allergens; Anti-Allergic Agents; Cedrus; Conjunctiva; Conjunctivitis, Allergic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Humans; Hyperemia; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Platelet Aggregation Inhibitors; Pollen; Rhinitis, Allergic, Seasonal; Young Adult

The objective of this study was to compare the efficacy and safety of olopatadine versus epinastine in healthy Japanese adults with a history of allergic conjunctivitis to Japanese cedar pollen.. This Phase IV double-blind randomized controlled clinical trial comprised three clinical visits over 30 days. Screening tests were performed to identify subjects with a history of allergic conjunctivitis to Japanese cedar pollen in terms of skin sensitivity and positive bilateral reactions to a conjunctival allergen challenge (CAC) with Japanese cedar pollen at Visit 1, and confirmation by a positive bilateral CAC reaction at Visit 2. At Visit 3, the subjects were randomized to receive one drop of olopatadine HCl ophthalmic solution 0.1% (olopatadine) in the left or right eye (1:1 ratio). All subjects received one drop of epinastine HCl ophthalmic solution 0.05% (epinastine) in the contralateral eye as an active control. Five min later, the subjects underwent bilateral CAC tests with one drop of the allergen solution at the concentration that elicited positive reactions at Visits 1 and 2. Efficacy outcomes included the severity of ocular itching at 5, 7, and 15 min and the severity of conjunctival hyperemia at 7, 15, and 20 min after the CAC test, as graded by the investigator by biomicroscopy.. Fifty people participated in this study (25 per group). Olopatadine significantly reduced ocular itching at 7 and 15 min (both p<0.05) and conjunctival hyperemia at 7 and 20 min (p=0.0010 and p<0.05, respectively) after allergen exposure compared with epinastine. There were no adverse events for either treatment.. The results of this single-dose study suggest that olopatadine is superior to epinastine in terms of suppressing ocular itching and hyperemia induced by Japanese cedar pollen during CAC tests. Further studies are needed to confirm these findings in real-life settings.

Topics: Adult; Allergens; Anti-Allergic Agents; Conjunctivitis, Allergic; Cryptomeria; Dibenzazepines; Double-Blind Method; Female; Humans; Imidazoles; Japan; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Pollen; Severity of Illness Index; Skin Tests; Treatment Outcome

We aimed to compare the clinical efficacy and ocular surface variables of olopatadine, ketotifen fumarate, epinastine, emedastine and fluorometholone acetate ophthalmic solutions in preventing the signs and symptoms of seasonal allergic conjunctivitis (SAC).. This was a prospective, randomized, double-blinded and placebo-controlled study. A total of 100 patients with SAC were randomly assigned to one of five groups, in which they were administered olopatadine, ketotifen fumarate, epinastine, emedastine or fluorometholone acetate, instilled twice daily for 2 weeks. One eye of each patient was treated with the study drug and the other was treated with a placebo. Signs and symptoms of allergic conjunctivitis (itching, redness, tearing, chemosis and eyelid swelling) were scored on a 4-point scale. Each symptom was assessed at baseline and then again after 1 and 2 weeks of treatment. Ocular surface variables were assessed by conjunctival impression cytology.. At weeks 1 and 2, all antiallergic agents were significantly more effective than placebo in alleviating itching, redness, tearing, chemosis and eyelid swelling. Fluorometholone acetate was significantly less effective than the other agents in reducing itching and redness at all control visits. Ocular surface findings by impression cytology improved significantly after all treatments compared with placebo.. In patients with SAC, olopatadine, ketotifen, epinastine and emedastine are more efficacious than fluorometholone acetate in preventing itching and redness. All the antiallergic agents gave similar results in terms of reducing tearing, chemosis and eyelid swelling. Our data showed that impression cytology parameters improved after treatment with antiallergic agents in patients with SAC.

Topics: Adolescent; Adult; Anti-Allergic Agents; Benzimidazoles; Child; Conjunctival Diseases; Conjunctivitis, Allergic; Dibenzazepines; Dibenzoxepins; Double-Blind Method; Edema; Eyelid Diseases; Female; Fluorometholone; Histamine H1 Antagonists; Humans; Imidazoles; Ketotifen; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Prospective Studies; Pruritus; Seasons; Tears; Treatment Outcome; Young Adult

Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H(1) antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis.. To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC).. This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12 h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5 min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4. MAIN OUTCOME MEASURES;. This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7 min and redness was assessed at 7, 15, and 20 min post-challenge. Drop comfort was assessed upon instillation, at 30s, and at 1, 2, and 5 min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 (p = 0.024) and 7 min (p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p < or = 0.013, conjunctival: p < or = 0.015, episcleral: p < or = 0.006). Olopatadine 0.2% was rated as significantly more comfortable than epinastine 0.05% at 1 min post-drop instillation (p = 0.003). All adverse events were non-serious and unrelated to study medication. Although the CAC model reproduces allergic responses that are not environmentally-induced, patients experience varying severities of responses as are seen in real-world situations.. Olopatadine 0.2% was superior to epinastine 0.05% in preventing ocular itching and redness at onset when induced by the CAC model.

Topics: Adolescent; Adult; Aged; Allergens; Color; Conjunctivitis, Allergic; Dibenzazepines; Dibenzoxepins; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Patient Satisfaction; Placebos; Pruritus; Treatment Outcome

This post hoc analysis used data from a previous study to more precisely evaluate the efficacy of olopatadine hydrochloride and epinastine hydrochloride in alleviating various levels of severity of ocular itching and conjunctival redness and to determine whether there were any significant differences in the number of responders to treatment.. The original study was a randomized, double-masked allergen challenge comparison assessment. Adult patients with allergic conjunctivitis were screened (visits 1 and 2); those who exhibited positive allergic reactions at both visits were randomized to 1 of 3 groups. olopatadine/epinastine, olopatadine/placebo, or epinastine/placebo. At visit 3, each eye was treated with study medication, and then challenged with allergen. Itching, redness, and chemosis assessments were recorded. For the present post hoc analysis, each eye in the olopatadine/epinastine group was separately classified at each time point, based on the pretreatment severity of their symptom (itching) and sign (conjunctival redness) scores, as moderate, moderate/severe, or severe. Data were analyzed to determine responders (eyes with itching and/or conjunctival redness scores of 0 [none]).. Of 96 patients screened, 66 were randomized to treatment (36 women, 30 men; mean age, 44.38 years [range, 20-71 years]). Olopatadine-treated eyes exhibited lower mean itching scores than epinastine-treated eyes in the moderate/severe and severe groups at all 3 time points (3, 5, and 7 minutes), with significance in the moderate/severe group at 5 minutes (P = 0.05) and in the severe group at 5 and 7 minutes (P = 0.017 and P = 0.02, respectively). Olopatadine-treated eyes had mean conjunctival redness scores similar to epinastine-treated eyes in all severity groups at all time points (10, 15, and 20 minutes) except in the severe group at 10 minutes (P = 0.03). On response analysis, for itching, the proportion of responders was significantly greater in the olopatadine group versus the epinastine group 7 minutes after challenge (27 [50.9%] vs 14 [26.4%]; P = 0.016). For conjunctival redness, the proportion of responders was significantly greater with olopatadine treatment versus epinastine treatment at 15 and 20 minutes after challenge (15 minutes, 12 [22.6%] vs 1 [1.9%] [P = 0.002]; 20 minutes, 10 [18.9%] vs 1 [1.9%] [P = 0.008]).

Topics: Adult; Aged; Dibenzazepines; Dibenzoxepins; Eye Diseases; Female; Humans; Hypersensitivity; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Placebos; Treatment Outcome

Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis.. This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model.. This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3 min, 5 min, and 7 min post challenge. Objective redness and chemosis assessments were made at 10 min, 15 min, and 20 min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments. MAIN OUTCOME MEASURES;. Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, -0.19 (p = 0.003) and -0.52 (p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis -0.24 (p < 0.001), ciliary redness -0.55 (p < 0.001), and episcleral redness -0.58 (p < 0.001) than epinastine treated eyes.. Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

Topics: Administration, Topical; Adult; Allergens; Anti-Allergic Agents; Conjunctivitis, Allergic; Diagnostic Techniques, Ophthalmological; Dibenzazepines; Dibenzoxepins; Double-Blind Method; Female; Humans; Imidazoles; Male; Models, Biological; Olopatadine Hydrochloride; Ophthalmic Solutions; Prospective Studies; Treatment Outcome

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

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 aim of this study was to compare the effect of topical olopatadine, epinastine, and lubricant eye drops on dry eye ocular surface disease in the botulinum toxin B (BTX-B)-induced mouse model of keratoconjunctivitis sicca.. CBA/J mice were randomized into 3 experimental groups of 10 animals each. All mice received a transconjunctival injection of 0.05 mL of 20-mU BTX-B solutions into the left lacrimal gland. Three (3) days after intralacrimal gland injections, each group received treatment with twice-daily topical lubricant as a control, 0.1% olopatadine, or 0.05% epinastine eye drops. To monitor the progression of dry eye tear production, an ocular surface fluorescein staining score was evaluated in each of the 3 experimental groups.. Three (3) days after the intralacrimal gland injection of BTX-B, aqueous tear production was significantly decreased (1.95+/-0.64 mm), compared to baseline level (2.69+/-0.66 mm; P<0.001). Similarly, there was a statistically significant increase in the proportion of mice with a corneal staining score of 2 or greater at 3 days postinjection, compared to the preinjection value (P<0.001). There were no statistically significant differences in aqueous tear production between the 3 different medication groups at all time points. Aqueous tear production in neither the olopatadine nor the epinastine-challenged groups was further decreased compared to the lubricant-treated group. Difference in the proportion of mice with a low- and high corneal staining score between the control and study groups did not reach statistical significance throughout the 4-week experimental period. In addition, changes in corneal fluorescein staining of the olopatadine group versus the epinastine group did not show a statistically significant difference.. Topical olopatadine and epinastine do not cause significantly additional damage to the compromised ocular surface secondary to dry eye after continuous 4-week, twice-daily application. Topical olopatadine and epinastine appear to have comparable effects on aqueous tear-production and corneal-surface changes in this mouse model.

Topics: Administration, Topical; Animals; Botulinum Toxins; Botulinum Toxins, Type A; Dibenzazepines; Dibenzoxepins; Disease Models, Animal; Female; Histamine H1 Antagonists; Imidazoles; Keratoconjunctivitis Sicca; Mice; Mice, Inbred CBA; Olopatadine Hydrochloride; Tears

The topical application of 0.1% olopatadine has been shown to provide significant attenuation of histamine-induced conjunctival vascular permeability (CVP) within 5 min and for as long as 24 h following a topical administration. The duration of the action of olopatadine was compared to that of epinastine, azelastine, and ketotifen. Male Hartley outbred guinea pigs (weighing 250-300 g) were administered a drug or vehicle as single O.D. topical drops, at times ranging from 4 to 24 h prior to histamine challenge. One (1) h prior to histamine challenge, the animals were administered 1 mL of Evans blue dye (1 mg/mL) through the marginal ear vein. Histamine (300 ng) was administered by a subconjunctival injection, and the guinea pigs were sacrificed 30 min later. CVP was assessed as the area and color intensity stained with Evans blue dye. The potencies of each drug were determined by calculating a 50% effective dose (ED(50)) for the inhibition of vascular leakage, compared to vehicle treatment, at each time point. Olopatadine was the only compound tested that was significantly effective 16 h following a single topical application. The ED(50) for olopatadine at 16 h was 0.031%. Epinastine, azelastine, and ketotifen were only significantly effective for up to 4 h. Olopatadine exhibited the longest duration of action for inhibition of histamine-induced vascular permeability in guinea pigs of any topical antiallergic drug tested. Concentrations of olopatadine, which provided a greater than 50% inhibition of the histamine-induced vascular response, were consistently less than 0.1% over a 16-h pretreatment interval.

Topics: Administration, Topical; Animals; Anti-Allergic Agents; Capillary Permeability; Conjunctiva; Delayed-Action Preparations; Dibenzazepines; Dibenzoxepins; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Histamine H1 Antagonists; Imidazoles; Ketotifen; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Phthalazines

Conjunctival mast cells (MCs) are important effector cells in seasonal allergic conjunctivitis, via histamine and cytokine secretion. Several new anti-allergic eye drops stabilize MCs and block histamine receptors, but their anti-inflammatory effects are unclear.. Anti-allergic drugs were compared for their anti-inflammatory effects in an in vitro model of human MC activation and in an experimental murine model of allergic conjunctivitis.. Human cord blood stem cell-derived (CBMC) and conjunctival biopsy-derived MCs were stimulated via FcepsilonRI, degranulation and histamine release were assayed at 1 h and cytokine secretion at 24 h using multiplex arrays. Mice sensitized to short ragweed pollen were given anti-allergics topically before allergen challenge, and conjunctival immuno-staining was performed at 24 h.. After a 1 h stimulation, 80% of the CBMC had degranulated and secreted histamine (27.9+/-4.7 ng/10(6) cells; P<0.05). Pre-treatment by all drugs significantly reduced histamine and TNF-alpha, whereas IL-5, IL-8, IL-10 and TNF-beta profiles were differentially decreased. For conjunctival biopsy-derived cultures (n=11), FcepsilonR1 stimulation increased histamine, TNF-alpha, TNF-beta, IL-5 and IL-8 levels and the production of IL-5, IL-6 (P<0.05), histamine and IL-8 (P<0.01) was inhibited by epinastine. In vivo, epinastine and olopatadine pre-treatment significantly reduced the clinical scores and eosinophil numbers (n=6; P<0.05) while epinastine also reduced neutrophils (P<0.02).. Differential effects on MC cytokine inhibition were observed, with epinastine inhibiting MC secretion of IL-5, IL-8, IL-10 and conjunctival neutrophil infiltration. The anti-allergic drugs have anti-histamine and mast-cell stabilizing properties but might differ in clinical improvement depending on the individual and the cytokines involved.

Topics: Animals; Anti-Allergic Agents; Cell Differentiation; Cell Movement; Cells, Cultured; Conjunctiva; Conjunctivitis, Allergic; Cytokines; Dibenzazepines; Dibenzoxepins; Eosinophilia; Female; Fetal Blood; Histamine Release; Humans; Imidazoles; Mast Cells; Mice; Mice, Inbred BALB C; Nedocromil; Neutrophils; Olopatadine Hydrochloride; Pollen; Proto-Oncogene Proteins c-kit; Receptors, IgE; Stem Cells

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 effects of topical epinastine and olopatadine on tear volume by using a mouse model.. Eighty-five C57BL6 mice (170 eyes) were treated twice daily with topical ophthalmic epinastine 0.05%, olopatadine 0.1%, or atropine 1% or served as untreated controls. A thread-wetting assay was used to measure tear volume at baseline and 15, 45, 90, 120, and 240 minutes after the last instillation of the drug on days 2 and 4 of treatment.. After 2 days of treatment, epinastine-treated mice showed greater mean tear volumes than olopatadine-treated mice did at 15, 45, 90, and 240 minutes, with statistical significance at 15 and 45 minutes (P<0.001). Olopatadine significantly reduced tear volume versus untreated controls at 15 and 45 minutes (P<0.001). After 4 days, tear volumes with epinastine treatment exceeded those with olopatadine treatment at all time points, with statistical significance at 45 minutes (P<0.05). Atropine rendered tears undetectable at 15, 45, and 90 minutes; tear volume returned to baseline levels at 240 minutes.. Topical epinastine did not inhibit tear secretion, whereas olopatadine caused a significant decrease in tear volume. Because of its neutral impact on the lacrimal functional unit, epinastine may be an especially good choice for the treatment of allergic conjunctivitis in patients with dry eye disease or in those who are at risk for developing dry eye.

Topics: Administration, Topical; Animals; Conjunctivitis, Allergic; Dibenzazepines; Dibenzoxepins; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Imidazoles; Lacrimal Apparatus; Male; Mice; Mice, Inbred C57BL; Olopatadine Hydrochloride; Ophthalmic Solutions; Tears

Antiallergic drugs have various actions against allergy-associated cells and molecules as well as antihistamic properties. We studied the effects of antiallergics on the serum levels of substance P. Patients with atopic dermatitis were treated with one of four oral H1-antagonists for 14 days, and the serum level of substance P was measured before and after treatment in parallel with several atopic severity markers. Olopatadine significantly decreased the substance P level. This is in accordance with its known downmodulatory effect on tachykinin release. In contrast, cetiridine and fexofenadine unexpectedly increased the substance P level. In patients administered cetiridine, the blood severity markers for atopic dermatitis, including lactate dehydrogenase, eosinophil number, and the soluble forms of IL-2R, E-selectin, VCAM-1 and ICAM-1 were reduced after the treatment. Therefore, the elevation of SP was unrelated to the deterioration of atopic dermatitis but rather associated with improvement. Our study suggests that antiallergics can be divided into substance P-increasing and -decreasing types and raises the possibility that the increment of substance P by the former type is caused by the competitive occupation of substance P receptors.

Topics: Adult; Anti-Allergic Agents; Cetirizine; Dermatitis, Atopic; Dibenzazepines; Dibenzoxepins; E-Selectin; Female; Histamine H1 Antagonists; Humans; Imidazoles; Intercellular Adhesion Molecule-1; Male; Olopatadine Hydrochloride; Substance P; Terfenadine; Vascular Cell Adhesion Molecule-1