olopatadine-hydrochloride and Disease-Models--Animal

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

The alkali-induced corneal injury is an ocular emergency that required an immediate and effective management to preserve the normal corneal functions and transparency. Olopatadine is a fast, topically-effective anti-allergic drug, which exhibited potent anti-inflammatory and anti-angiogenic abilities in different allergic animals' models. Therefore, this study aimed to evaluate the therapeutic effect of olopatadine on alkali-induced corneal injury in rats.. Corneal alkali injury (CI) induced in the right eyes of an eight-week-old male Wister rats, by application of 3 mm diameter filter-papers, soaked for 10 s in 1 N-NaOH, to the right eyes' corneal centers for 30 s, afterward, the filter paper removed, and the rat right eye rinsed with 20 ml normal saline. For treatment of CI, either 0.2% or 0.77% olopatadine applied topically daily for 14 days, starting immediately after the induction of CI.. Olopatadine, in the present work, effectively and dose-dependently enhanced the corneal healing after alkali application, with significant reduction of the corneal opacity and neovascularization scores, besides, it suppressed the augmented corneal IL-1β, VEGF, caspase-3 levels, and nuclear NF-κB immunohistochemical expression, meanwhile it abrogated the corneal histopathological changes, induced by alkali application.. Olopatadine appears to be a potential treatment option for alkali-induced corneal injury.

Topics: Alkalies; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Burns, Chemical; Caspase 3; Cornea; Corneal Injuries; Disease Models, Animal; Hypersensitivity; Immunohistochemistry; Interleukin-1beta; Male; NF-kappa B; Olopatadine Hydrochloride; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A; Wound Healing

The aim of the current study was to investigate whether olopatadine and naphazoline hydrochloride reduce allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF. An allergic conjunctivitis mouse model was established using histamine or an antigen (ovalbumin), following which mice were treated with 1% olopatadine solution and/or 0.2 mg/ml of naphazoline hydrochloride. Histamine or antigen‑induced conjunctival vascular hyperpermeability was examined and the levels of inflammatory factors, cytokines, IgE, GMCSF and NGF were analyzed using ELISA in antigen‑induced conjunctival vascular hyperpermeability mice. In addition, VEGF protein expression was measured using western blotting in antigen‑induced mice. The results indicated that olopatadine and naphazoline hydrochloride significantly suppressed conjunctival dye leakage in mice with histamine or antigen‑induced conjunctival vascular hyperpermeability. In addition, treatment with olopatadine and naphazoline hydrochloride was able to reduce the levels of inflammatory factors (TNF‑α, IL‑1β and IL‑6), cytokines (IFN‑γ and IL‑4), IgE, GMCSF, and NGF in antigen‑induced conjunctival vascular hyperpermeability mice. The protein expression levels of VEGF in antigen‑induced conjunctival vascular hyperpermeability mice were reduced following treatment with olopatadine and naphazoline hydrochloride. These results suggest that treatment with olopatadine and naphazoline hydrochloride reduces conjunctivitis in mice via effects on inflammation, NGF and VEGF.

Topics: Animals; Blotting, Western; Conjunctivitis, Allergic; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine; Immunoglobulin E; Mice; Mice, Inbred BALB C; Naphazoline; Nerve Growth Factor; Olopatadine Hydrochloride; Ovalbumin; Vascular Endothelial Growth Factor A

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

This study was undertaken to evaluate possible antiallergic effects of an extract of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells. Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes allergic conjunctivitis, and rabbit local skin irritation. The extract significantly reduced, in a dose-dependent manner, the histamine-induced contractions of the isolated guinea pig ileum with ID50 =1.2 µg/mL (in equivalents of spinochrome B), had an inhibitory effect on the model of ocular allergic inflammation surpassing the reference drug olopatadine, and did not show any irritating effect in rabbits. The extract predominantly contained polyhydroxy-1,4-naphthoquinone which would be responsible for the pharmacological activity. The active compounds of the extract were evaluated in silico with molecular docking. Molecular docking into H1R receptor structures obtained from molecular dynamic simulations showed that all spinochrome derivatives bind to the receptor active site, but spinochrome monomers fit better to it. The results of the present study suggest possibilities for the development of new agents for treating allergic diseases on the base of pigments from sea urchins shells.

Topics: Animal Shells; Animals; Anti-Allergic Agents; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Ileum; Male; Molecular Docking Simulation; Naphthoquinones; Olopatadine Hydrochloride; Pigments, Biological; Rabbits; Skin; Strongylocentrotus

Topics: Animals; Cytokines; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Gene Expression; Histamine H1 Antagonists; Mice; Olopatadine Hydrochloride; Thymic Stromal Lymphopoietin

Although histamine H1 receptor (H1R) antagonists are commonly used to treat atopic dermatitis, the treatment is not always effective. The histamine H4 receptor (H4R) was recently described as important to the pruritus in dermatitis. Here, we investigated whether the combination of a H1R antagonist plus a H4R antagonist attenuates chronic dermatitis in NC/Nga mice.. Chronic dermatitis was developed by repeated challenges with picryl chloride on the dorsal back and ear lobes. The therapeutic effects of the H1R antagonist olopatadine and H4R antagonist JNJ7777120 on scratching and the severity of dermatitis were evaluated. In addition, the mechanisms responsible for the anti-allergic effects of H1R and/or H4R antagonism were examined using bone marrow-derived mast cells (BMMC) and keratinocytes.. JNJ7777120 attenuated scratching behavior after a single administration and improved dermatitis, as assessed with clinical scores, pathology, and cytokine levels in skin lesions when administered repeatedly. These effects were augmented by combined treatment with olopatadine, having a similar therapeutic efficacy to prednisolone. JNJ7777120 inhibited dose-dependently the production of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 from antigen-stimulated BMMC. In addition, olopatadine reversed the histamine-induced reduction of semaphorin 3A mRNA in keratinocytes.. Combined treatment with H1R and H4R antagonists may have a significant therapeutic effect on chronic dermatitis through the synergistic inhibition of pruritus and skin inflammation.

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Bone Marrow Cells; Chemokine CCL17; Chemokine CCL22; Cytokines; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Down-Regulation; Histamine; Histamine Antagonists; Histamine H1 Antagonists; Histamine Release; Immunoglobulin E; Indoles; Male; Mast Cells; Mice; Olopatadine Hydrochloride; Picryl Chloride; Piperazines; Receptors, Histamine H1; Semaphorin-3A

Histamine facilitates development of eczematous lesions in chronic allergic contact dermatitis. In addition to the well-known corticosteroid treatments, H1 receptor (H1R) antagonists also have been used. This study observed effects of histamine H4 receptor (H4R) antagonist usage with H1R antagonist in a murine chronic allergic contact dermatitis model, developed by repeated percutaneous challenge to the dorsal skin with 2,4,6-trinitro-1-chlorobenzene (TNCB). The H1R antagonist olopatadine hydrochloride and/or the H4R antagonist JNJ7777120 was then administered. Combination therapy was more effective than H1R antagonist monotherapy. Serum IgE and levels of interleukin (IL)-4, IL-5 and IL-6 (Th2 cytokines) in eczematous lesions decreased with combined therapy. Combined therapy with H1R and H4R antagonists counteracts the disadvantages of each as monotherapeutic agents and potentially represents a new strategy for the treatment of chronic allergic contact dermatitis.

Topics: Animals; Dermatitis, Allergic Contact; Dibenzoxepins; Disease Models, Animal; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Immunoglobulin E; Indoles; Interleukin-4; Interleukin-5; Interleukin-6; Mice; Mice, Inbred C57BL; Olopatadine Hydrochloride; Picryl Chloride; Piperazines; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4

Antihistamines constitute the first line of therapy for allergic conjunctivitis, and are safe and effective in relieving the signs and symptoms of ocular allergy. Despite this, they are less effective than some other drugs in relieving delayed symptoms of allergic conjunctivitis. Recent evidence suggests that changes in the conjunctival epithelium may underlie aspects of delayed reactions. In this study we compared two antihistamines, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.. Studies employed a modified conjunctival allergen challenge model. Sensitized mice were challenged with topical allergen with or without drug treatments. Treatment groups were assayed for acute-phase (15 minutes) and delayed-phase (24 hours) responses. Groups were scored for allergy symptoms (redness, itch, tearing, and edema) and for conjunctival mast cell numbers. Delayed-phase groups were also examined for eosinophil numbers and for tight junctional protein expression.. Olopatadine-treated and alcaftadine-treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase. In contrast, alcaftadine-treated animals had significantly lower conjunctival eosinophil infiltration than either controls or olopatadine-treated animals. Allergen challenge caused a significant decrease in expression of the junctional protein, ZO-1, and this decrease was prevented by alcaftadine but not by olopatadine.. Alcaftadine displays therapeutic properties beyond its antihistamine action. These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression.

Topics: Animals; Anti-Allergic Agents; Benzazepines; Conjunctiva; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Eosinophils; Epithelium; Gene Expression Regulation; Imidazoles; Membrane Proteins; Mice; Mice, Inbred BALB C; Olopatadine Hydrochloride; Phosphoproteins; Tight Junctions; Time Factors; Zonula Occludens-1 Protein

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

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

It is well known that starting treatment for cedar pollinosis therapy with second-generation antihistamines before the initial day of pollen scattering can relieve nasal symptom severity during the pollen season. Olopatadine hydrochloride (olopatadine) is an antiallergic agent with histamine H(1) receptor antagonistic action. We have evaluated the effects of repeated preadministration of olopatadine on the toluene-2,4-diisocyanate-induced rhinitis in rats. A single administration of olopatadine suppressed sneezing and the increases in histamine, nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) production in nasal lavage fluid. When olopatadine was administered repeatedly once a day for 7 days before provocation, its inhibitory effects were enhanced compared to the effect of a single administration. Although the repeated administration of fexofenadine enhanced the inhibitory effects on sneezing, it did not inhibit the increases in NGF and VEGF production. These results show that the suppression of the increase in NGF and VEGF might partially be involved in the improvement of nasal allergy signs by the treatment with olopatadine. It is expected that the early treatment with olopatadine may achieve stable therapeutic effects.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Dibenzoxepins; Disease Models, Animal; Drug Administration Schedule; Histamine H1 Antagonists, Non-Sedating; Male; Nerve Growth Factor; Olopatadine Hydrochloride; Rats; Rats, Inbred BN; Rhinitis, Allergic, Seasonal; Terfenadine; Toluene 2,4-Diisocyanate; Vascular Endothelial Growth Factor A

In order to compare the relative efficacy of topical antihistamines with balanced saline solution (BSS) and benzalkonium chloride (BC) in the early phase of allergic conjunctivitis in an animal model of ocular anaphylaxis, 96 male guinea pigs were sensitized with intraperitoneal egg albumin (EA) and aluminum hydroxide. Seventy-six animals were used for determination of Evans blue (EB) extravasation and 20 for clinical evaluation of the allergic response (redness, edema, discharge and itch-scratch response). Eighteen days after sensitization the animals were topically challenged by conjunctival instillation of EA and treated 15 min before and 15 min after challenge with commercially available drugs (ketotifen, ketotifen single dose units [SDU], olopatadine, azelastine, spaglumic acid and emedastine) and controls (BSS and BC). The animals used for EB quantification were anesthetized and received an intravenous injection of EB simultaneously to the topical challenge. The ocular extravasation of the colorant was determined by 620 nm absorbance spectrophotometry. The animals used for clinical evaluation were observed for clinical signs of the allergic reaction. EB ocular extravasation was significantly lower in the eyes treated by spaglumic acid and emedastine. The clinical scoring was consistent with EB extravasation, though the difference was not statistically significant. Spaglumic acid and emedastine seem to be the most useful drugs to reduce EB extravasation and allergic signs in an animal model of early phase allergic conjunctivitis.

Topics: Animals; Anti-Allergic Agents; Benzimidazoles; Coloring Agents; Conjunctivitis, Allergic; Dibenzoxepins; Dipeptides; Disease Models, Animal; Drug Evaluation, Preclinical; Evans Blue; Guinea Pigs; Histamine H1 Antagonists; Ketotifen; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Phthalazines; Severity of Illness Index; Treatment Outcome

The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. In patients with AR, levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) increase. Olopatadine hydrochloride (olopatadine) is an anti-allergic agent with histamine H1 receptor antagonistic action. To investigate whether olopatadine has an effect on inflammatory reactions, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as an animal model of nasal allergy. Nasal allergy signs (sneezing, rhinorrhea and inflammation) were induced after TDI challenge. Amounts of NGF and VEGF in the nasal lavage fluid increased. Olopatadine reduced nasal allergy signs and inhibited increases in NGF and VEGF. These findings suggest that the increases in NGF and VEGF production are involved in the mechanism responsible for nasal allergy signs in TDI-challenged rats. Other histamine H1 receptor antagonists did not inhibit and instillation of histamine did not increase TDI-induced NGF and VEGF production. Therefore, olopatadine appears to exert additional biological effects other than its blockade of the histamine H(1) receptor. These results suggest that suppression of neurogenic inflammatory reactions might be partially involved in the improvement of allergy signs after treatment with olopatadine.

Topics: Animals; Anti-Allergic Agents; Dibenzoxepins; Disease Models, Animal; Histamine; Histamine H1 Antagonists, Non-Sedating; Male; Nasal Lavage Fluid; Nerve Growth Factor; Olopatadine Hydrochloride; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic, Perennial; Toluene 2,4-Diisocyanate; Vascular Endothelial Growth Factor A

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

To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats.. Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control.. At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine.. In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.

Topics: Anaphylaxis; Animals; Capillary Permeability; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Edema; Eyelids; Guinea Pigs; Histamine H1 Antagonists; Ketotifen; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Ovalbumin; Piperidines; Rats

Olopatadine hydrochloride is an H1-receptor-blocker but has other anti-allergic pharmacological potencies. We investigated whether olopatadine inhibits murine contact hypersensitivity, focussing on its modulatory action on epidermal Langerhans cells serving as antigen-presenting cells. While BALB/c mice were sensitized and challenged epicutaneously with hapten, they were administered intraperitoneally with olopatadine. Olopatadine at 1 or 0.2 mg/kg of weight significantly suppressed the sensitivity when injected at least once before sensitization or challenge. In olopatadine-injected mice, the ability of Langerhans cells to present hapten to primed T cells was reduced with decreased expression of MHC class II and co-stimulatory molecules. Langerhans cells exposed in vitro to 10(-5) or 10(-6) M olopatadine had less antigen-presenting activity than control, whereas neither T cell proliferation nor keratinocyte production of IL-1alpha and IP-10 was affected at these doses. These findings suggest that olopatadine downmodulates contact hypersensitivity at least partly by interfering with the antigen-presenting ability of Langerhans cells.

Topics: Animals; Anti-Allergic Agents; Antigen Presentation; Antigens, Surface; Cells, Cultured; Chemokine CXCL10; Dermatitis, Contact; Dibenzoxepins; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Epidermis; Female; Haptens; Histocompatibility Antigens Class II; Interleukin-1; Keratinocytes; Langerhans Cells; Mice; Mice, Inbred BALB C; Olopatadine Hydrochloride; T-Lymphocytes

We investigated the effect of KW-4679 (Z-11-(dimethylaminopropyliden)-6,11-dihydrodibenzoxepin-2-a cetic acid hydrochloride), an antiallergic agent, on the nasal blockage induced by antigen challenge into the nostrils of actively sensitized guinea pigs. The change of the nasal cavity volume caused by nasal mucosal swelling after antigen challenge was measured by acoustic rhinometry. Oral administration of KW-4679 (0.01-10 mg/kg) significantly inhibited the decrease in the nasal cavity volume at 10 min, 30 min and 6 hr after antigen challenge. Ketotifen (1-10 mg/kg, p.o.) also inhibited the decrease in the nasal cavity volume after antigen challenge. These results indicate that KW-4679 may be useful for the treatment of allergic rhinitis.

Topics: Animals; Dibenzoxepins; Disease Models, Animal; Guinea Pigs; Male; Nasal Cavity; Nasal Obstruction; Olopatadine Hydrochloride; Rhinitis; Time Factors