Kenji Ohmori

KYOWA HAKKO BIO Co., Ltd., Edo, Tōkyō, Japan

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Publications (55)78.61 Total impact

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    ABSTRACT: Background: Various mediators, such as thromboxane (TX) A2, peptide leukotrienes (P-LT) and histamine, are involved in allergic nasal obstruction. The aim of the present study was to investigate the mechanism whereby olopatadine hydrochloride, a novel anti-allergic drug, ameliorated the allergic nasal obstruction.Methods: The levels of TXB2, P-LT and histamine in nasal lavage fluid (NLF) were measured after intranasal antigen challenge in sensitized guinea pigs.Results: Histamine and TXB2 levels in the NLF increased eight- and threefold, respectively, 10 min after antigen challenge, whereas the P-LT level was under the detection limit. Oral administration of olopatadine at 0.1, 1 and 3 mg/kg significantly inhibited the increases in TXB2 and histamine levels. At 3 mg/kg, olopatadine also ameliorated the nasal obstruction caused 10 min after antigen challenge, as determined by acoustic rhinometry.Conclusions: These results suggest that the amelioration by olopatadine of the allergic nasal obstruction involves the inhibition of the release of TXA2 and histamine.
    Allergology International 06/2008; 50(4):337 - 341. DOI:10.1046/j.1440-1592.2001.00236.x
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    ABSTRACT: Olopatadine hydrochloride (olopatadine; KW-4679), (Z)-11-[(3-dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid monohydrochloride, is an antiallergic drug with selective and potent histamine H1 receptor antagonist activity. In the present study, we investigated the effect of olopatadine on the release of peptide leukotrienes (P-LT), potent inflammatory mediators, from human eosinophils. Human eosinophils were purified from venous blood of healthy donors by negative selection using the anti-CD16 antibody. When human eosinophils were stimu- lated with the calcium ionophore A23187 (1 μmol/L), the amount of P-LT release was approximately 1200 pg/ 105 cells, while thromboxane (TX) B2 release was under the detection limit (< 20 pg/105 cells). Olopatadine inhibited the A23187-induced P-LT release from human eosinophils with an IC50 of 4.5 μmol/L. Ketotifen also inhibited this reaction with an IC50 of 39.4 μmol/L. The inhibitory effect of olopatadine on the P-LT release may contribute to the antiallergic efficacy of this drug.
    Allergology International 06/2008; 50(1):113 - 116. DOI:10.1111/j.1440-1592.2001.00207.pp.x
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    ABSTRACT: Maxillary sinus carcinoma (MSC) is a rare disease with a variety of treatment options. The present study was undertaken to review the outcome of patients with treated MSC in order to clarify the factors related to local recurrence by analyzing CT findings. The study group comprised of 47 cases, 40 males and 7 females with a median age of 61 years (range, 40- 84 years) treated between 1988 to 1996 at the department of radiotherapy. CT was taken with a slice thickness of 5 mm and contrast material was routinely used. The mean follow-up period for the group was 45.0 months (range, 3-125 months). The treatment policy was either preoperative radiotherapy of 40Gy/16fr followed by maxillectomy or radical radiotherapy of 65Gy/26fr with partial maxillectomy during the course of radiotherapy. By using CT-simulation, wedge pair techniques were used in most patients with Cobalt or 6MV X-ray machines as treatment sources. Tumor extension was categorized into the following anatomical sites: orbital contents, other paranasal sinuses, posterior wall of the maxillary sinus, pterygoid plate/muscle, nasopharynx, infra-temporal fossa, base of the skull, anterior wall of the maxillary sinus, subcutaneous tissue, cheek mucosa, hard palate and alveolar bone. Local control was computed by using the Kaplan-Meier method and p value was measured by using Chi-squared test. The 5-year overall local control rates for all patients were 56%. The local recurrence was found in 19 of 47 patients (40.4%). Tumors extending to pterygoid plates (n=13) and pterygoid muscles (n=10) showed higher rate of local recurrences as compared to those without extensions (9/13 [69%] vs 10/34 [29%], p<0.02 and 7/10 [70%] vs 12/37 [32%], p<0.05, respectively). Extensions to nasopharynx (6/9, 66%) and base of skull (4/6, 66%) also showed higher rates of recurrence; however, those were not statistically significant. More than 80% of the relapse became manifest within 12 months of diagnosis and isolated local failure was the most common pattern. This analysis indicates that tumor extension to pterygoid plate/muscles, results in higher rates of recurrences. This may due to the difficult surgical accessibility of the tumor. During radiotherapy planning, special emphasis should be given to this sites of tumor extension to avoid possible local recurrence.
    Mymensingh Medical Journal 07/2006; 15(2):188-91. DOI:10.3329/mmj.v15i2.42
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    ABSTRACT: Olopatadine hydrochloride (olopatadine) is an antiallergic drug with histamine H(1) receptor antagonistic activity. Recently, olopatadine has been shown to bind to S100A12 which is a member of the S100 family of calcium-binding proteins, and exerts multiple proinflammatory activities including chemotaxis for monocytes and neutrophils. In this study, we examined the possibility that the interaction of olopatadine with S100A12 inhibits the proinflammatory effects of S100A12. Pretreatment of olopatadine with S100A12 reduced migration of THP-1, a monocyte cell line, induced by S100A12 alone, but did not affect recombinant human regulated upon activation, normal T cell expressed and secreted (RANTES)-induced migration. Amlexanox, which also binds to S100A12, inhibited the THP-1 migration induced by S100A12. However, ketotifen, another histamine H(1) receptor antagonist, had little effect on the activity of S100A12. These results suggest that olopatadine has a new mechanism of action, that is, suppression of the function of S100A12, in addition to histamine H(1) receptor antagonistic activity.
    Mediators of Inflammation 02/2006; 2006(1):42726. DOI:10.1155/MI/2006/42726 · 2.42 Impact Factor
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    ABSTRACT: Histamine stimulates the release of several cytokines, such as interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor, from bronchial epithelial cells. However, the functional individual histamine receptor subtype and intracellular signaling in bronchial epithelial cells are poorly defined. Using human primary epithelial cells and the NCI-H292 cell line, we examined the expression of histamine receptor subtypes and histamine-induced second messenger. We also evaluated the involvements of mitogen-activated protein kinase, protein kinase C (PKC) and epidermal growth factor receptor in cytokine expression caused by histamine. Histamine H1 receptor (H1R) was the only subtype expressed in both types of cells. Histamine elevated intracellular calcium ion without affecting cAMP levels. Histamine induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Histamine also phosphorylated PKC and myristoylated alanine-rich C kinase substrate. Ro-31-8220, a PKC inhibitor, and PD98059, a mitogen-activated protein/ERK kinase inhibitor, suppressed the histamine-induced ERK activation and the production of granulocyte macrophage colony-stimulating factor and IL-8. On the contrary, histamine had no effect on the phosphorylation of epidermal growth factor receptor, and its specific inhibitor AG1478 failed to inhibit the histamine-induced ERK activation. Olopatadine, an H1 antagonist, completely blocked the histamine-related responses, whereas H2 and H3 antagonists did not. Histamine also augmented the IL-8 production caused by IL-4 or tumor necrosis factor-alpha. The H1R-PKC-ERK pathway may play crucial roles in eliciting cytokine production from bronchial epithelial cells stimulated by histamine, leading to airway inflammation.
    International Archives of Allergy and Immunology 02/2006; 139(4):279-93. DOI:10.1159/000091599 · 2.43 Impact Factor
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    ABSTRACT: Histamine H1 receptor antagonists have long been prescribed for atopic dermatitis as an adjuvant therapy with topical therapy by local applied steroids. Olopatadine is one of the second-generation histamine H1 receptor antagonists that are treated for allergic disorders. We investigated that the effect of olopatadine on oxazolone-induced chronic contact hypersensitivity response in BALB/c mice compared with other histamine H1 receptor antagonists loratadine, cetirizine and fexofenadine. The chronic contact hypersensitivity induced by repeated application of oxazolone was treated with olopatadine and other histamine H1 receptor antagonists at the effective doses on histamine-induced paw edema in mice. The effects of these drugs in the oxazolone-induced model were quantified by measurements of ear swelling, and levels of cytokines in the lesioned ear. Olopatadine significantly inhibited the ear swelling and the increased production of IL-4, IL-1beta, IL-6, GM-CSF and NGF in the lesioned ear. On the other hand, the other histamine H1 receptor antagonists did not significantly suppress the increase in ear thickness. Moreover, they did not affect the production of cytokines in the lesioned ear. These results indicate that olopatadine appears to exert additional biological effects besides its blockade of the histamine H1 receptor.
    Pharmacology 01/2006; 75(1):45-52. DOI:10.1159/000086272 · 1.58 Impact Factor
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    ABSTRACT: 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.
    European Journal of Pharmacology 12/2005; 524(1-3):149-54. DOI:10.1016/j.ejphar.2005.09.004 · 2.68 Impact Factor
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    ABSTRACT: Histamine H1 receptor (H1R), a therapeutic target for alleviation of acute allergic reaction, may be also involved in mediating inflammatory responses via effects on cytokine production. However, the mechanisms whereby histamine induces cytokine production are poorly defined. In this study, we comprehensively investigated the signaling pathway involved in cytokine expression caused by histamine, using native human epidermal keratinocytes. We confirmed the expression of functional H1R by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and histamine-induced Ca(2+) elevation. Histamine induced concentration- and time-dependent production of granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-8 and IL-6, which was completely blocked by olopatadine, an H1 antagonist. Histamine activated the phosphorylation of protein kinase C (PKC), c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), I kappa B kinase (IKK), inhibitory kappa B (I kappa B)-alpha and nuclear factor-KB (NF-kappa B) p65, which was inhibited by Ro-31-8220, a PKC inhibitor. Also, Ro-31-8220 significantly suppressed the expression of these cytokines. BAPTA-AM, an intracellular Ca(2+) chelator, also reduced PKC phosphorylation and cytokine expression. PD98059, a MEK inhibitor, and BAY 11-8702, an I kappa B-alpha inhibitor, reduced ERK and NF-kappa B cascade activation, respectively, with little effect on PKC phosphorylation. PD98059 preferentially inhibited GM-CSF production whereas BAY 11-8702 prevented IL-8 and IL-6 production. Furthermore, in addition to the above cytokines, histamine stimulated the biosynthesis and/or release of numerous keratinocyte-derived mediators, which are probably regulated by the ERK or NF-kappa B cascades. Our study suggests that histamine activates Ca(2+)-dependent PKC isoforms that play crucial roles in the activation of Raf/MEK/ERK and IKK/I kappa B/NF-kappa B cascades, leading to up-regulation of cytokine expression. Thus, the anti-inflammatory benefit of H1 antagonists may be in part due to prevention of cytokine production.
    Biochemical Pharmacology 03/2005; 69(3):433-49. DOI:10.1016/j.bcp.2004.10.006 · 4.65 Impact Factor
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    ABSTRACT: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.
    Clinical & Experimental Allergy 02/2005; 35(1):97-103. DOI:10.1111/j.1365-2222.2005.02147.x · 4.32 Impact Factor
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    ABSTRACT: Olopatadine hydrochloride (olopatadine) is one of the second-generation antihistamines, which is prescribed for allergic disorders such as rhinitis, urticaria and eczema dermatitis. To investigate the possible anti-inflammatory effect of olopatadine on the chronic contact hypersensitivity response to repeated topical application of oxazolone in mice. The preventive and therapeutic effects of oral olopatadine were quantified by measurements of ear swelling, cytokine protein and mRNA expression in the ear lesion, and were compared with those of topical betamethasone 17-valerate (betamethasone). The ear receiving repeated applications of oxazolone exhibited erythema, oedema and abrasion. Both preventive and therapeutic administration of olopatadine (10 mg kg(-1) day(-1)) significantly inhibited the ear swelling and the increased production of interleukin (IL)-4, IL-1beta, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor. In the histopathological analysis, olopatadine ameliorated epidermal hyperplasia and infiltration of inflammatory cells. Consistent with these results, olopatadine significantly reduced the increased expression of interferon-gamma and IL-4 mRNA. Although betamethasone (0.012 mg ear(-1) day(-1)) showed similar activities to olopatadine against these responses, it caused atrophy of the ear skin. These results indicate that olopatadine is an antihistamine agent having inhibitory activities against chronic inflammatory dermatitis, possibly resulting from its diminishing effect on elevated cytokines.
    British Journal of Dermatology 01/2005; 151(6):1133-42. DOI:10.1111/j.1365-2133.2004.06172.x · 4.10 Impact Factor
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    ABSTRACT: Due to the prevalence of allergic diseases such as bronchial asthma, allergic rhinoconjunctivitis and dermallergosis, efforts at the discovery of novel and effective medications for prevention and treatment of these conditions have been reinforced. Recently, it has been recognized that these allergic diseases are a chronic inflammatory disorder of the lower and upper airways and skin. In this article, we reviewed the recent development of the following new antiallergic therapies: anti-Th2 cytokine antibodies, decoy receptors, receptor antibodies, anti-IgE antibodies, anti-cell adhesion molecules antibodies, antisense oligonucleotides, keratinocyte modulators, inhibitors of phosphodiesterase 4, tachykinin receptor antagonists, and anti-histaminic drugs. Most of these new agents are aimed to inhibit various components of allergic inflammation. The future use of allergic disease therapies hold great promise and excitement.
    Folia Pharmacologica Japonica 06/2004; 123(5):335-48. DOI:10.1254/fpj.123.335
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    ABSTRACT: Olopatadine hydrochloride (olopatadine) is an anti-allergic drug that functions as a histamine H(1) antagonist and inhibits both mast cell degranulation and the release of arachidonic acid metabolites in various types of cells. In this study, we examined the ability of olopatadine to inhibit the expression of cytokine genes in vitro via high-affinity receptors for immunoglobulin E in mast cells, using a rat basophilic leukemia (RBL-2H3) cell line and an in vivo mouse model. Levels of gene expression in RBL-2H3 cells were determined by semi-quantitative RT-PCR, and serum interleukin-4 (IL-4) level in mice was quantified by ELISA. Olopatadine inhibited significantly the induction of IL-4 expression by mast cells both in vivo and in vitro. Olopatadine inhibited Ca(2+) influx through receptor-operated channels (ROC) without affecting Ca(2+) release from intracellular stores. Comparative analysis of olopatadine with other anti-allergic drugs and the ROC blocker SKF-96365 demonstrated that the potency of inhibition of Ca(2+) influx correlated with the degree of suppression of degranulation and arachidonic acid release. Inhibition of Ca(2+) influx decreased phosphorylation of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase, which participate in regulation of cytokine (e.g. IL-4) gene expression. However, the rank order of inhibition of Ca(2+) influx did not correspond to reduction of IL-4 expression, suggesting that an unknown mechanism(s) of action, in addition to inhibition of Ca(2+) influx, is involved in the expression of cytokines in mast cells.
    Biochemical Pharmacology 05/2004; 67(7):1315-26. DOI:10.1016/j.bcp.2003.12.008 · 4.65 Impact Factor
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    ABSTRACT: Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that 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 inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritus, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.
    Arzneimittel-Forschung 02/2004; 54(12):809-29. DOI:10.1055/s-0031-1297036 · 0.51 Impact Factor
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    ABSTRACT: Background: Olopatadine hydrochloride is an anti-allergic agent with histamine H1 receptor antagonistic action. We investigated the effects of olopatadine on passive anaphylaxis reaction- and compound 48/80-induced conjunctivitis in rats.Methods: Allergic conjunctivitis was induced in rats passively sensitized by injection of rat anti-ovalbumin (anti-OVA) serum into the upper subconjunctiva of the right eye, followed by intravenous administration of the antigen and Evans blue dye. After 30 min, the amount of dye leaking into the conjunctiva was measured. Non-allergic conjunctivitis was induced in rats by injection of compound 48/80. Olopatadine or other reference compounds were orally given 1 h before the challenge.Results: The amount of dye leaking into the ­conjunctiva following passive anaphylaxis was ­significantly inhibited by oral administration of 0.01−1 mg/kg olopatadine and the ID50 value was 0.093 mg/kg. In the control group, pathological examination revealed edema and lymphocyte infiltration in the conjunctiva and the pal­pebral skin. Olopatadine, at 0.03 and 0.3 mg/kg, reduced the grade of these pathological findings. The other antiallergic drugs (1 mg/kg loratadine, 0.3 mg/kg epinastine, 0.3 mg/kg cetiridine, 1 mg/kg ebastine, 30 mg/kg fexofenadine and 3 mg/kg chlorpheniramine), when administered orally, inhibited the passive anaphylaxis reaction-induced vascular hyperpermeability of the conjunctiva, as was the case with olopatadine hydrochloride. Subconjunctival administration of compound 48/80 induced vascular hyper­permeability, which is presumably mediated by histamine release. Oral administration of 0.1 and 1 mg/kg olopatadine significantly inhibited the amount of dye leakage.Conclusion: Orally administered olopatadine is expected to improve allergic conjunctivitis.
    Allergology International 03/2003; 52(2):77-83. DOI:10.1046/j.1440-1592.2003.00281.x
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    ABSTRACT: Diacerein has proved to be effective in the treatment of osteoarthritis. We investigated the effects of diacerein in animal models of carrageenin-, zymosan-, or dextran-induced paw edema and adjuvant-induced arthritis and in ovariectomized rats. In acute inflammatory models, unlike classical nonsteroidal anti-inflammatory drugs such as naproxen and ibuprofen, diacerein inhibited the rat paw edema induced by various agents. In the adjuvant-induced arthritic rats, diacerein at 100 mg/kg/day significantly suppressed the paw edema and the increase in serum mucoprotein. Addition of 3 mg/kg/day naproxen to each diacerein (3, 10, 30 mg/kg/day) dose resulted in significantly greater anti-inflammatory activity than with naproxen alone. In the ovariectomized rats, diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum alkaline phosphatase and decreased the excretion of urinary hydroxyproline. In addition, rhein (10, 30 microM) inhibited calcium release from mouse calvaria induced by interleukin-1 beta, prostaglandin E(2) and parathyroid hormone 1-34 human fragment. These findings indicate that diacerein is a novel anti-inflammatory drug with pharmacological properties different from those of classical nonsteroidal anti-inflammatory drugs and support the clinical investigation of the use of combination therapy with diacerein and nonsteroidal anti-inflammatory drugs in patients with not only osteoarthritis but also rheumatoid arthritis.
    European Journal of Pharmacology 08/2002; 448(1):81-7. DOI:10.1016/S0014-2999(02)01898-8 · 2.68 Impact Factor
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    ABSTRACT: 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).
    The Japanese Journal of Pharmacology 05/2002; 88(4):379-97. DOI:10.1254/jjp.88.379
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    ABSTRACT: Erdosteine (CAS 84611-23-4) and its active metabolite (M1) decrease the luminol-dependent chemiluminescence (LDCL). In this study, the scavenging effects of erdosteine and M1 on each reactive oxygen species, hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and superoxide anion (O2-), were investigated. M1 interacted with HOCl at high activity, whereas erdosteine exhibited low activity. Although erdosteine interacted with H2O2 only at 1 mmol/l, M1 could significantly decrease H2O2 (> 0.1 mmol/l). Erdosteine and M1 did not interact with O2-. These results suggest that M1 possesses scavenging activities against H2O2 and HOCl in vitro.
    Arzneimittel-Forschung 01/2002; 52(6):435-40. DOI:10.1055/s-0031-1299911 · 0.51 Impact Factor
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    ABSTRACT: 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.
    The Japanese Journal of Pharmacology 11/2001; 87(2):167-70. DOI:10.1254/jjp.87.167
  • International Journal of Radiation OncologyBiologyPhysics 11/2001; 51(3):340-340. DOI:10.1016/S0360-3016(01)02450-6 · 4.18 Impact Factor
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    ABSTRACT: We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.
    European Journal of Pharmacology 09/2001; 425(3):219-27. DOI:10.1016/S0014-2999(01)01177-3 · 2.68 Impact Factor

Publication Stats

593 Citations
78.61 Total Impact Points

Institutions

  • 2002–2006
    • KYOWA HAKKO BIO Co., Ltd.
      Edo, Tōkyō, Japan
  • 1998–2001
    • Hokkaido University
      • Department of Dentistry
      Sapporo, Hokkaidō, Japan
  • 1999
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan