olopatadine-hydrochloride and Pruritus

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

Olopatadine hydrochloride (olopatadine, 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid monohydrochloride) is a novel antiallergic/histamine H1-receptor antagonistic drug that was synthesized and evaluated in our laboratories. Oral administration of olopatadine at doses of 0.03 mg/kg or higher inhibited the symptoms of experimental allergic skin responses, rhinoconjunctivitis and bronchial asthma in sensitized guinea pigs and rats. Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig ventricular myocytes, myocardium and human ether-a-go-go-related gene channel. Olopatadine was highly and rapidly absorbed in healthy human volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was considerably low in the clearance of olopatadine in humans. Olopatadine is one of the few renal clearance drugs in antiallergic drugs. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. Ophthalmic solution of olopatadine was also approved in the United States for the treatment of seasonal allergic conjunctivitis in December, 1996 (Appendix: also in the European Union, it was approved in February 2002).

Topics: Animals; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Conjunctivitis, Allergic; Dibenzoxepins; Drug Administration Routes; Histamine H1 Antagonists; Humans; Hypersensitivity; Inflammation Mediators; Olopatadine Hydrochloride; Ophthalmic Solutions; Pruritus; Rhinitis, Allergic, Perennial; Urticaria

Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine inhibited passive cutaneous anaphylaxis in rats, experimental allergic rhinitis and bronchial asthmatic responses in actively sensitized guinea pigs. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig myocardium and ventricular myocytes. Olopatadine was highly and rapidly absorbed in healthy volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was low in the elimination of olopatadine. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000.

Topics: Animals; Anti-Allergic Agents; Clinical Trials as Topic; Depression, Chemical; Dibenzoxepins; Histamine H1 Antagonists; Humans; Inflammation Mediators; Olopatadine Hydrochloride; Passive Cutaneous Anaphylaxis; Pruritus; Rhinitis, Allergic, Perennial; Urticaria

Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E

Topics: Adolescent; Adult; Aged; Allergens; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine Antagonists; Histamine H1 Antagonists; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Pruritus; Retrospective Studies; Treatment Outcome; Young Adult

We have demonstrated for the first time that a second-generation antihistamine ameliorates nocturnal scratching behavior in atopic dermatitis patients using a modified wristwatch-type acoustic scratching counting system that we have recently developed. We also analyzed the sleep quality by simultaneous recording of electroencephalogram, and found that sleep quality was unaffected.

Topics: Dermatitis, Atopic; Double-Blind Method; Electroencephalography; Histamine H1 Antagonists, Non-Sedating; Humans; Olopatadine Hydrochloride; Pruritus; Severity of Illness Index; Sleep Stages; Time Factors; Visual Analog Scale

The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated.. Pooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score<1) and zero itch (itch score=0) was also assessed.. A total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P=0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P=0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P<0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P=0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported.. Once-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated.

Topics: Adult; Allergens; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Drug Monitoring; Female; Humans; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Patient Outcome Assessment; Pruritus

The antihistamine effects of olopatadine and levocetirizine, in standard-dose application described in their information (5 mg twice a day for olopatadine; 5 mg once daily for levocetirizine), were examined from 11.5 to 24 h after application. The test was designed in a double-blind, randomized, cross-over, placebo-controlled study of 12 healthy volunteers on histamine-induced flare and wheal response using an iontophoresis technique. The suppressive effect of olopatadine on the wheals induced by a 0.1-mA histamine iontophoresis lasted for 24 h after dosing. Both drugs inhibited flare induced by histamine iontophoresis almost completely until 24 h after the first administration. Suppression of the 0.2-mA-induced wheal response by levocetirizine, taken once daily, decreased with time, although 0.1-mA-induced flare was almost completely suppressed by the drug. Olopatadine completely suppressed even the wheal response induced by a 0.2-mA histamine iontophoresis. Compared with the placebo, the two drugs significantly suppressed the subjective itching assessed by visual analog scale at all intervals. There were no significant differences in subjective drowsiness and objective cognitive function between drug- and placebo-treated subjects. These results demonstrate that olopatadine seems to be more potent than levocetirizine when administrated in a standard dose. In conclusion, mild to moderate urticaria could be controlled by standard application as described in their information. On the other hand, severe urticaria could be managed by a standard application of olopatadine, but levocetirizine may need an additional dose to control severe urticaria.

Topics: Adult; Cetirizine; Cognition; Cross-Over Studies; Dibenzoxepins; Double-Blind Method; Female; Healthy Volunteers; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Iontophoresis; Male; Middle Aged; Olopatadine Hydrochloride; Pruritus; Sleep Stages; Young Adult

An increased dose of the prescribed drug or a change of the drug is recommended in the treatment for the patients with urticaria refractory to the standard dose of antihistamines. Efficacy and safety of doubling the dose of cetirizine were compared with olopatadine in the patients with symptoms like wheal or itching, despite the treatment with the standard dose of cetirizine.. Cetirizine was administered at 10 mg once daily to 51 patients with urticaria for a mean of 10.1 ± 7.3 days (period A). Patients with inadequate responses were randomized to either cetirizine 20 mg once daily (dose-increase group) or olopatadine 5 mg twice daily (drug-change group) for a mean of 13.3 ± 8.3 days (Period B). The severity of wheal and itching, and the quality of life (QOL) measured by Skindex-16 were evaluated.. In period A, an adequate response was obtained in 64.7% (33/51). Nine patients each with inadequate response were randomized to either the drug-change or dose-increase groups. A significant improvement was observed in the severity of wheal and itching in the dose-increase group in period B. The QOL was significantly improved in all sub-scales of Skindex-16.. Doubling the dose of cetirizine may be efficacious to the patients with urticaria refractory to the regular dose of cetirizine.

Topics: Adolescent; Adult; Anti-Allergic Agents; Cetirizine; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Prospective Studies; Pruritus; Quality of Life; Treatment Outcome; Urticaria

To assess whether olopatadine hydrochloride (OH) was noninferior to cetirizine in the treatment of cutaneous pruritus (CP).. Patients with CP presenting at seven centers in China were randomly allocated to double-blind treatment with 5 mg of OH orally twice a day or cetirizine 10 mg orally once a day for 2 weeks. Patients were followed up on days 7 and 14. Noninferiority was predefined as a 20% maximum difference in the reduction of symptom score reducing indices (SSRI). Both intention-to-treat (ITT) and per-protocol populations were analyzed.. 174 patients (86 receiving OH and 88 cetirizine) were included in the ITT population. In the ITT population, the mean reduction in SSRI was 0.640 ± 0.274 in the OH group and 0.603 ± 0.289 in the cetirizine group. The one-sided 97.5% CI (-0.047) met the criteria for noninferiority. Noninferiority was also demonstrated for SSRI in the per-protocol population, with reductions of 0.640 ± 0.271 with OH and 0.596 ± 0.287 with cetirizine (97.5% CI -0.043).The total effectiveness rate (TER) was similar in the OH (90.0%) and cetirizine (80.0%) groups. The corresponding one-sided 97.5% CI (-1.0%) also demonstrated noninferiority. The incidence of adverse events was 47.1% in the OH group and 41.4% in the cetirizine group (p = 0.453).. The efficacy of OH was noninferior to that of cetirizine in controlling itching indicating that it can be considered as a clinically relevant alternative therapy to cetirizine for the management of CP in adult Chinese patients.

Topics: Adult; Anti-Allergic Agents; Asian People; Cetirizine; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Pruritus; Treatment Outcome; Young Adult

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients' quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.

Topics: Adolescent; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Male; Olopatadine Hydrochloride; Promethazine; Pruritus; Psychomotor Performance; Rhinitis, Allergic, Seasonal; Terfenadine; Urticaria; Young Adult

Olopatadine hydrochloride ophthalmic solution, 0.2% (olopatadine 0.2%) is approved for allergic conjunctivitis when instilled twice-daily. The objective of this study was to evaluate the efficacy and safety of olopatadine 0.2% (instilled twice-daily) versus vehicle and olopatadine 0.1% (instilled 4-times daily) in Japanese patients with allergic conjunctivitis.. A multicenter, parallel-group, double-masked, randomized, conjunctival allergen challenge (CAC) study. Patients > or = 18 years of age with histories of allergic conjunctivitis were treated with either olopatadine 0.2% or olopatadine 0.1% in a single eye and the vehicle in the contralateral eye at 1 visit.. Overall, 267 patients were enrolled. Olopatadine 0.2% was superior to its vehicle for ocular itching (p < 0.0001 at the time of observation) and marginally superior for total redness (p = 0.0543 at the time of observation). Olopatadine 0.2% was similar to olopatadine 0.1% for ocular itching at the time of observation. No trends were identified through a review of safety parameters.. Olopatadine 0.2% (instilled twice-daily) is safe, well tolerated, superior to the vehicle, and similar to olopatadine 0.1% in preventing ocular itching. Olopatadine 0.2%, which can be instilled less often than olopatadine 0.1%, is a useful new option for allergic conjunctivitis in Japanese patients that could potentially result in better treatment compliance.

Topics: Adolescent; Adult; Anti-Allergic Agents; Conjunctivitis, Allergic; Dibenzoxepins; Female; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Pruritus; Treatment Outcome; Young Adult

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

Atopic dermatitis (AD) is a common chronic or chronically relapsing, severely pruritic, eczematous skin disease. Recently, substance P (SP) has been demonstrated to be one of the important neuropeptides for mediating itch-scratch and stress-scratch cycles. In this study, we examined the severity scores, itch scores and plasma SP levels in 19 patients with AD treated with standard topical therapy with or without an oral antihistamine, olopatadine hydrochloride, for 4 weeks. The standard therapy decreased SCORAD scores, itch behavioral rating scores and plasma SP levels at post-treatment in the mass, but the topical therapy with olopatadine was more effective than the topical therapy alone, suggesting a potential additive effect.

Topics: Administration, Oral; Administration, Topical; Adult; Dermatitis, Atopic; Dibenzoxepins; Drug Synergism; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Olopatadine Hydrochloride; Pruritus; Substance P; 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

Olopatadine 0.1% (Patanol) and olopatadine 0.2% (Pataday) ophthalmic solutions are topical ocular anti-allergic agents with antihistaminic and mast cell stabilizing properties. The efficacy of two doses of olopatadine 0.1% was compared to one dose of olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis over 24 hours. This double-masked conjunctival allergen challenge (CAC) study found no significant difference in the mean itching scores between two drops of olopatadine 0.1% and one drop of olopatadine 0.2%. Both showed significant activity at the 24-hour time point and were statistically superior to placebo. No adverse events occurred while on drug therapy.

Topics: Adult; Allergens; Conjunctiva; Conjunctivitis, Allergic; Dibenzoxepins; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Pruritus; Skin Tests; Treatment Outcome

Topical antiallergic agents, such as antihistamines and mast-cell stabilizers, are the main therapeutic options for seasonal allergic conjunctivitis (SAC). Ketotifen fumarate and olopatadine HCl have dual action that offers a combination of these 2 mechanisms. Although clinical studies comparing the efficacy of these 2 drugs have shown that both were effective in the treatment of SAC, the results were contradictory and did not include the effects of these drugs on inflammatory markers.. The aims of this study were to compare the clinical efficacy of topical ketotifen and olopatadine eye drops and to determine the effects of these 2 drugs on the expression of cell adhesion molecules (CAMs) and inflammatory markers in conjunctival surface cells in patients with SAC.. This 30-day, randomized, double-masked, artificial tear substitute (ATS)-controlled clinical trial was conducted at the Department of Ophthalmology, Karadeniz Technical University, School of Medicine, Trabzon, Turkey. Patients with SAC were included in the study and randomly assigned to 1 of 3 groups: topical ketotifen fumarate 0.025% ophthalmic solution, topical olopatadine HCl 0.1% ophthalmic solution, or ATS (control group). All drugs were administered 2 drops per eye BID for 30 days. At the beginning of the study (day 0; baseline), on day 15, and on day 30, clinical scores (itching, tearing, redness, eyelid, swelling, and chemosis) and conjunctival impression cytology specimens were obtained. The percentages of cells expressing intercellular adhesion molecule 1, vascular CAM-1, human leukocyte antigen-DR, and beta1-integrin (CD29) from conjunctival impression cytology specimens were determined using flow cytometry. Patients were questioned about adverse events (AEs) at each visit. Ocular discomfort on installation of the drugs was recorded as an AE.. Thirty-nine patients (20 men, 19 women; age range, 18-61 years) with SAC were included. Twelve patients received ketotifen; 13, olopatadine; and 14, ATS. In both active-treatment groups, the improvements of clinical scores (tearing and itching) were more pronounced compared with those in the ATS group, although the day-30 difference in tearing score between the olopatadine and ATS groups was not statistically significant. No significant within-group or between-group differences in mean scores for redness, chemosis, or eyelid swelling were found. The expression rates of CAMs and inflammatory markers in conjunctival surface cells were significantly more reduced with ketotifen and olopatadine compared with ATS. However, clinical and flow cytometric parameters were improved with ATS at 15 and 30 days compared with baseline. No AEs were observed during the study period.. In this short-term study in a selected, small study population with SAC, ketotifen and olopatadine diminished the expression of CAMs and inflammatory markers on the conjunctival surface cells effectively. Both active treatments were more efficacious compared with ATS and were well tolerated.

Topics: Adolescent; Adult; Anti-Allergic Agents; Cell Adhesion Molecules; Conjunctiva; Conjunctivitis, Allergic; Dibenzoxepins; Female; HLA-DR Antigens; Humans; Integrin beta1; Ketotifen; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Pruritus; Seasons; Tears; Time Factors

Itch is a major indicator of psoriasis, but the underlying mechanisms behind this symptom are largely unknown. To investigate the neuronal mechanisms of psoriatic itch, we tested whether mice subjected to the imiquimod-induced psoriasis model exhibit itch-associated behaviors. Mice received daily topical applications of imiquimod to the rostral back skin for 7 days. Imiquimod-treated mice exhibited a significant increase in spontaneous scratching behavior directed to the treated area as well as touch-evoked scratching (alloknesis). To characterize this model, we measured the mRNA expression levels of pruritogens and itch-relevant receptors/channels using real-time reverse transcription PCR. The mRNA expression of MrgprA3, MrgprC11, and MrgprD decreased gradually over time in the dorsal root ganglion (DRG) cells. There was no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells. TRPV4 mRNA expression was transiently increased in the DRG cells, whereas TRPM8 mRNA was significantly decreased. The mRNA expression levels of histidine decarboxylase and tryptophan hydroxylase 1, as well as the intensity of histamine and serotonin immunoreactivity, were transiently increased in the skin on day 2, returning to baseline by day 7. Histamine H1-receptor antagonists, chlorpheniramine and olopatadine, significantly inhibited spontaneous scratching on day 2, but not day 7. Neither chlorpheniramine nor olopatadine affected alloknesis on day 2 or day 7. These results may reflect the limited antipruritic effects of histamine H1-receptor antagonists on human psoriasis. The imiquimod-induced psoriasis model seems to be useful for the investigation of itch and its sensitization in psoriasis.

Topics: Adjuvants, Immunologic; Aminoquinolines; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipruritics; Chlorpheniramine; Disease Models, Animal; Ganglia, Spinal; Gene Expression Regulation; Histidine Decarboxylase; Imiquimod; Male; Mice; Mice, Inbred C57BL; Olopatadine Hydrochloride; Pain Measurement; Pruritus; Random Allocation; Skin; TRPV Cation Channels; Tryptophan Hydroxylase

Topics: Animals; Anti-Allergic Agents; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Immunosuppressive Agents; Interleukins; Mice; Olopatadine Hydrochloride; Pruritus; Tacrolimus

Control of itch is an important issue in the treatment of atopic dermatitis (AD). Itch is mediated by a variety of pruritogens, including histamine, and promoted by neurite outgrowth in the epidermis of AD patients, probably due to the release of nerve growth factor.. We investigated the effects of orally administered olopatadine hydrochloride (olopatadine) on itching, itching mediators, and neuritogenic action in a mouse model.. NC/Nga mice were treated topically with Dermatophagoides farinae body (Dfb) extract twice weekly for 4 weeks to induce AD-like lesions. They were concomitantly given oral olopatadine, distilled deionized water, or topical tacrolimus during the last 2 weeks.. Olopatadine significantly suppressed scratching, improved the dermatitis score, inhibited neurite outgrowth, and decreased the elevated inflammatory markers, growth factors and histamine content in the lesional skin, and serum concentration of Dfb-specific IgE. Notably, olopatadine treatment increased semaphorin 3A expression in the epidermis.. Our study confirms the pleiotropic effects of olopatadine, i.e. inhibition of inflammation and neurite extension into the epidermis.

Topics: Animals; Cytokines; Dermatitis, Atopic; Dermatophagoides farinae; Dibenzoxepins; Disease Models, Animal; Female; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Mice; Nerve Growth Factor; Neurites; Olopatadine Hydrochloride; Pruritus; Rats; Rats, Wistar; Semaphorin-3A; Th2 Cells

We investigated the synergetic effects of glucocorticoid and histamine H1 receptor antagonists on an atopic dermatitis model. Hairless mice were used in this study and an atopic dermatitis model was made by repeated application of 2,4,6-trinitrochlorobenzene. The effects of glucocorticoid, histamine H1 receptor antagonists, and the simultaneous use of these drugs were investigated by measuring scratching behavior, skin symptoms and nerve growth factor (NGF) in the skin. Topical application of prednisolone significantly inhibited scratching behavior, skin symptoms and NGF contents in the skin by repeated application. Olopatadine also showed a significant effect on scratching behavior and NGF contents in the skin, whereas chlorpheniramine showed no significant inhibitory effect on these indices. Furthermore, the combined use of prednisolone and olopatadine potentiated the inhibition of scratching behavior, skin symptoms, and NGF in the skin. From these findings, olopatadine potentiated the inhibitory effect of prednisolone on the symptoms of atopic dermatitis by inhibiting NGF.

Topics: Allergens; Animals; Antipruritics; Behavior, Animal; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Glucocorticoids; Histamine H1 Antagonists; Male; Mice; Mice, Hairless; Nerve Growth Factor; Olopatadine Hydrochloride; Picryl Chloride; Prednisolone; Pruritus; Severity of Illness Index; Skin; Time Factors

The expression of nerve growth factor (NGF) is known to increase in the skin of patients with atopic dermatitis (AD) and is related to disease aggravation. In the present study, we measured skin NGF levels in AD patients and determined whether they correlate to AD severity as well as treatment effects.. NGF in the horny layer (horn NGF) of skin lesions found on the cubital fossa of AD patients was collected via tape stripping and measured using ELISA before and after 2 and 4 weeks following initiation of treatments. Itching and eruptions on the lesions were also evaluated. Peripheral blood eosinophil count, serum LDH level and total serum IgE level were also examined.. The level of NGF was significantly higher in AD patients than in healthy controls, and correlated with the severity of itch, erythema, scale/xerosis, eosinophil count, and LDH level. The NGF level decreased significantly at 2 and 4 weeks of treatment with olopatadine, a histamine H(1) receptor antagonist, and/or topical steroid. The reduction in NGF correlated with the decrease in the severity of itching and erythema, papule, scale/xerosis and lichenification of the lesion, eosinophil count, and LDH level. In psoriatic lesional skin with itch, the horn NGF was significantly higher than in non-lesional skin of psoriasis, but the value was lower than NGF in atopic skin.. The level of horn NGF was found to reflect the severity of itching and eruptions in AD. Therefore, quantification of NGF in the samples collected directly from the horny layer appears to be useful in assessing severity and therapeutic effects in AD.

Topics: Adult; Case-Control Studies; Dermatitis, Atopic; Dibenzoxepins; Epidermis; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Immunoglobulin E; L-Lactate Dehydrogenase; Male; Nerve Growth Factor; Olopatadine Hydrochloride; Pruritus; Psoriasis; Severity of Illness Index; Treatment Outcome

Topics: Animals; Antipruritics; Behavior, Animal; Dibenzoxepins; Disease Models, Animal; Dose-Response Relationship, Drug; Mice; Mice, Inbred C57BL; Oligopeptides; Olopatadine Hydrochloride; Protein Precursors; Pruritus; Receptor, PAR-2; RNA, Messenger; Substance P; Tachykinins; Time Factors

Intense pruritus and cutaneous reactivity represent cardinal features of eczema. The resulting scratching behaviors alter neuronal conditions of the spinal dorsal horn where the primary sensory afferent fibers transmit cutaneous stimulation and deteriorate eczematous skin lesions. We investigated the effects of olopatadine hydrochloride (olopatadine) on alteration of neuronal conditions of the spinal dorsal horn and eczematous skin lesions induced by contact dermatitis. Eczematous lesions were induced by repeated application of diphenylcyclopropenone (DCP) in BALB/c mice. Olopatadine suppressed scratching behavior caused by repeated application of DCP in mice. Increased expressions of c-Fos and substance P in the spinal dorsal horn following DCP application were improved by olopatadine. Furthermore, olopatadine diminished the number of infiltrating cells and levels of cytokines in eczematous skin lesions resulting from DCP application. Olopatadine improves neurological conditions in the spinal cord and eczematous skin lesions in a murine contact dermatitis model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cyclopropanes; Dermatitis, Contact; Dibenzoxepins; Dose-Response Relationship, Drug; Eczema; Female; Histamine H1 Antagonists; Immunohistochemistry; Mice; Mice, Inbred BALB C; Neurons; Olopatadine Hydrochloride; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Pruritus; Skin; Substance P

The clinical effects of second generation antihistamines on pruritus caused by various skin diseases were examined by keeping a daily record of their effects.. Five mg of olopatadine hydrochloride (Allerock) was administered to the subjects twice daily. The severity of the pruritus and the scratch scars were scored before, and then 2 weeks and 4 weeks after, commencement of treatment. The severity of the pruritus during the day and night was measured by using a visual analogue scale (VAS), and a daily 'itch score' was recorded in an 'itch diary.'. The itch scores for both day and night, as well as the scratching scores, the VAS values and the 'itch score,' significantly decreased after administration of olopatadine. The VAS value was significantly correlated with the itch scores and patient responses in the medical interview. Statistical analysis showed that there was a prompt alleviation of the pruritus in urticaria a day after administration, followed by asteatotic dermatitis and atopic dermatitis, in the order of improvement, within the next several days.. The VAS value for pruritus was highly correlated with the itch score, showing that the VAS value was suitable for evaluating daily changes in the severity of pruritus. These results suggest that second generation antihistamines like olopatadine hydrochloride, which showed a prompt response to histamine, are effective against pruritus in urticaria, and that continuous use of these antihistamines is effective against pruritus in other forms of skin disease, such as asteatotic dermatitis and atopic dermatitis in which other chemical mediators besides histamine may be the triggers for pruritus.

Topics: Adult; Antipruritics; Dermatitis, Atopic; Dibenzoxepins; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Pruritus

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.

Topics: Animals; Anti-Inflammatory Agents; Antipruritics; Chlorpheniramine; Cytokines; Dermatitis, Contact; Dibenzoxepins; Dose-Response Relationship, Drug; Ear; Histamine H1 Antagonists; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nerve Growth Factor; Olopatadine Hydrochloride; Oxazolone; Prednisolone; Pruritus; Severity of Illness Index

Intradermal injections of poly-L-arginine induce cutaneous vascular hyperpermeability and scratching behavior in rats. Recently, we elucidated that the plasma extravasation involved both histamine and substance P, while the scratching behavior involved substance P, but not histamine. This study examined the effects of olopatadine hydrochloride (olopatadine), an antiallergic drug with histamine H1-antagonistic action, on the poly-L-arginine-induced responses. Olopatadine (1 mg/kg, p.o.) significantly inhibited both the plasma extravasation and the scratching behavior, suggesting that its inhibitory effects are mediated by the suppression of neuropeptidergic action as well as histaminic action. Olopatadine seems to be a novel-type drug for the treatment of dermatitis.

Topics: Animals; Anti-Allergic Agents; Behavior, Animal; Capillary Permeability; Dibenzoxepins; Histamine H1 Antagonists; Male; Microcirculation; Olopatadine Hydrochloride; Peptides; Pruritus; Rats; Rats, Wistar; Skin; Tachykinins

Topics: Adult; Child; Child, Preschool; Conjunctivitis, Allergic; Dibenzoxepins; Histamine H1 Antagonists; Humans; Olopatadine Hydrochloride; Ophthalmic Solutions; Pruritus