The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform

Naosuke Matsuura - One of the best experts on this subject based on the ideXlab platform.

  • Suplatast tosilate, a new type of Antiallergic Agent, prevents the expression of airway hyperresponsiveness in guinea pigs
    European journal of pharmacology, 1996
    Co-Authors: Hajime Taniguchi, Hiroichi Nagai, Michinori Togawa, Katsuo Ohwada, Mamoru Kiniwa, Naosuke Matsuura, Akihide Koda
    Abstract:

    Suplatast tosilate (suplatast) is an Antiallergic Agent capable of down-regulating the functions of CD4+ T cells. We now investigated the effects of suplatast on the antigen-induced airway hyperresponsiveness and the underlying allergic inflammatory response in sensitized guinea pigs. Animals that had been immunized twice by ovalbumin inhalation on day 0 and day 7 developed an increased airway responsiveness against inhaled acetylcholine 24 h after the ovalbumin challenge on day 14. Suplatast (10 and 100 mg/kg per day) and ketotifen (10 mg/kg per day) given orally from day 0 to day 14 effectively inhibited the expression of airway hyperresponsiveness. They also inhibited the infiltration of eosinophils and macrophages into broncho-bronchiolar walls and lumen. Interestingly, suplatast, but not ketotifen, inhibited the infiltration of lymphocytes including CD4+ T cells. Collectively, these results strongly suggest that suplatast prevents the expression of airway hyperresponsiveness due to the ability to suppress the infiltration of inflammatory cells into lung tissues.

  • Down-regulation of Th2 cell-mediated murine peritoneal eosinophilia by Antiallergic Agents.
    Life sciences, 1995
    Co-Authors: Hidetoshi Yamaya, Michinori Togawa, Mamoru Kiniwa, Yuuji Basaki, Michiyo Kojima, Naosuke Matsuura
    Abstract:

    Abstract Local eosinophilia has been linked to the pathogenesis of the inflammatory aspect of allergic diseases. The present study found that co-injection of D10G4.1 (D10) cells, a murine Th2 clone, with conalbumin (CA) into the peritoneal cavity of AKR/J mice increased the number of peritoneal eosinophils. The accumulation of eosinophils reached a maximum level at 24 to 48 hr and was accompanied by a marked increase in the number of neutrophils and a minor increase in the number of mononuclear cells. D10-induced peritoneal eosinophilia was suppressed by administration of either anti-IL-4 and anti-IL-5 monoclonal antibodies in an additive manner or by cyclosporin A (CsA). Interestingly, suplatast tosilate (IPD-1151T), known to be an Antiallergic Agent capable of suppressing IgE synthesis and chemical mediator release, but not disodium cromoglycate, selectively suppressed eosinophil accumulation. Taken together with the observation that CsA and IPD-1151T suppressed IL-4 and IL-5 production by CA-stimulated D10 cells in vitro, the present results strongly suggest that Agents capable of down-regulating Th2 cell cytokine production may attenuate allergic inflammation by impairing the recruitment of eosinophils that is mediated by Th2 cells.

Hideo Kato - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacological studies on the novel Antiallergic Agent HSR-609: its effects on behavior in mice and electroencephalograms in rabbits.
    Japanese journal of pharmacology, 1997
    Co-Authors: Masato Kakiuchi, Tetsuo Ohashi, Kazuo Tanaka, Kazuko Kamiyama, Kouji Morikawa, Hideo Kato
    Abstract:

    ABSTRACT We studied the central nervous system (CNS) effects of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid dihydrate), a novel amphoteric Antiallergic Agent having antihistaminic activity. Its effects on the behavior of mice and the electroencephalograms (EEG) of unanesthetized and unrestrained rabbits after oral administration were compared with those of typical Antiallergic Agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz[b]oxepino[4,3-b]pyridine), which has a chemical structure similar to that of HSR-609. HSR-609 (3–300 mg/kg) had no effect on general behavior, spontaneous locomotor activity, hexobarbital-induced sleeping time and reserpine-induced hypothermia in mice. HSR-609 (10–100 mg/kg) and terfenadine (100 mg/kg) had no effect on spontaneous EEG, sleep-wakefulness cycles and EEG power spectra in rabbits. On the other hand, cyproheptadine (3–30 mg/kg), ketotifen (30–100 mg/kg) and PY-608 (0.3–100 mg/kg) caused increases and/or decreases of spontaneous locomotor activity, prolongation of hexobarbital-induced sleeping time and antagonistic effects on reserpine-induced hypothermia in mice. These Agents (30 mg/kg) increased slow wave sleep and enhanced EEG power spectra at low frequency bands such as δ and θ in rabbits. These findings suggest that HSR-609 has no inhibitory effect on the CNS due to its amphoteric chemical structure.

  • Studies on the novel Antiallergic Agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor.
    Japanese journal of pharmacology, 1997
    Co-Authors: Masato Kakiuchi, Tetsuo Ohashi, Kouji Morikawa, Hideo Kato, Keiichi Musoh, Kimio Kawamura
    Abstract:

    Abstract We studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5,ll-dihydro-benz[Z?]oxepino[4,3-b]pyridin-ll-ylidene)-piperidino]propionic acid dihydrate), a novel amphoteric Antiallergic Agent, on the central nervous system (CNS). Its selectivity for the histamine Hi-receptor and its ability to penetrate into the CNS were compared with those of typical Antiallergic Agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,ll-dihydro-ll-(l-methyl-4-piperidylidene)benz[b]oxepino-[4,3-b]pyridine), which has a chemical structure similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity for H1receptors in the guinea pig cerebral cortex in comparison to affinities for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while the selectivity of PY-608 for the Hi-receptor was low. The inhibitory effects of these Antiallergic Agents on histamine-induced increase of vascular permeability in mice (ED50) were compared with the displacement of [3H]mepyramine binding to H1-receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was much larger than those of cyproheptadine, ketotifen and PY-608 and larger than those of terfenadine and cetirizine. HSR-609 was found to display selective displacement of the [3H]mepyramine binding to H1receptors for lung vs cerebral cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest that HSR-609 has high selectivity for the H preceptor and poor ability to penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical structure.

  • Amphoteric drugs. 3. Synthesis and Antiallergic activity of 3-[(5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11- ylidene)piperidino]propionic acid derivatives and related compounds.
    Journal of medicinal chemistry, 1995
    Co-Authors: Nobuhiko Iwasaki, Tetsuo Ohashi, Hideo Kato, Keiichi Musoh, Yasuo Ito, Hiroyuki Nishino, Noriyuki Kado, Shingo Yasuda
    Abstract:

    An important approach to the design of Antiallergic Agents with reduced penetration into the central nervous system (CNS) is described. A series of 3-[(5,11- dihydro[1]benzoxepino[4,3-b]-pyridin-11-ylidene)piperidino]propion ic acid derivatives (31-47) and related compounds (48-54) were synthesized and evaluated for Antiallergic activity and penetration of a compound into the CNS in comparison with the corresponding 6H-dibenz[b,e]oxepin derivative (3). Combination of zwitterionization and introduction of a pyridine component resulted in an increase in Antiallergic activity and a great reduction of penetration into the CNS, which was evaluated by the selectivity (B/A) of antihistaminic activities in the central system [ID50 value (B) for ex vivo H1 binding to mouse brain membranes] and in the peripheral system [ED50 value (A) for inhibitory effect on histamine-induced increase in vascular permeability in mice]. This surprising reduction of penetration into the CNS could be considered on the basis of an increase in hydrophilicity caused by both of the zwitterionization and the introduction of a pyridine component. 3-[4-(8-Fluoro-5,11-dihydro[1]benzoxepino[4,3- b]pyridin-11-ylidene)piperidino]propionic acid (33) exhibited a strong Antiallergic effect in various experimental models and very low penetration into the CNS. Compound 33 (HSR-609) is now under clinical trial as a promising Antiallergic Agent with greatly reduced penetration into the CNS.

  • study on zwitter ionization of drugs ii synthesis and pharmacological activity of some n 3 5h dibenzo a d cyclohepten 5 ylidene propyl n methylamino and n 3 6h dibenz b e oxepin 11 ylidene propyl n methylamino alkanoic acid derivatives and related co
    Chemical & Pharmaceutical Bulletin, 1993
    Co-Authors: Hiromi Muramatsu, Masato Kakiuchi, Tetsuo Ohashi, Hideo Kato, Nobuhiko Iwasaki, Hiroyuki Sawanishi, Y Ito
    Abstract:

    A series of N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino- (6a) and N-[3-(6H-dibenz-[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic acid derivatives (6b) and related compounds (6c-f) were synthesized and examined for pharmacological activities in vitro, i.e., inhibitory effect on monoamine [noradrenaline (NA) and 5-hydroxytryptamine (5-HT)] uptake, inhibitory effect on 5-HT-, histamine-, acetylcholine- and NA-induced contraction, and binding affinity for α2-adrenoceptor and dopamine D2-receptor. In vitro tests indicated that zwitter-ionization was capable of maintaining H1-antihistaminic activity while greatly reducing other pharmacological activities. Further, 6a-f showed much stonger inhibitory effects on compound 48/80-induced lethality in rats than did the corresponding N, N-dimethylamines (2a-f). 3-[N-[3-(6H-Dibenz[b, e]oxepin-11-ylidene)propyl]-N-methylamino]-propionic acid (6b-2), selected as a candidate Antiallergic Agent of a new type, equally potent in rats and guinea-pigs, exhibited strong inhibitory effects on 48 h homologous passive cutaneous anaphylaxis (PCA) in rats (ED50=0.019 mg/kg, p.o.) and on histamine-induced bronchoconstriction in anesthetized guinea-pigs (ED50=0.0067 mg/kg, p.o.).

Tetsuo Ohashi - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacological studies on the novel Antiallergic Agent HSR-609: its effects on behavior in mice and electroencephalograms in rabbits.
    Japanese journal of pharmacology, 1997
    Co-Authors: Masato Kakiuchi, Tetsuo Ohashi, Kazuo Tanaka, Kazuko Kamiyama, Kouji Morikawa, Hideo Kato
    Abstract:

    ABSTRACT We studied the central nervous system (CNS) effects of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid dihydrate), a novel amphoteric Antiallergic Agent having antihistaminic activity. Its effects on the behavior of mice and the electroencephalograms (EEG) of unanesthetized and unrestrained rabbits after oral administration were compared with those of typical Antiallergic Agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz[b]oxepino[4,3-b]pyridine), which has a chemical structure similar to that of HSR-609. HSR-609 (3–300 mg/kg) had no effect on general behavior, spontaneous locomotor activity, hexobarbital-induced sleeping time and reserpine-induced hypothermia in mice. HSR-609 (10–100 mg/kg) and terfenadine (100 mg/kg) had no effect on spontaneous EEG, sleep-wakefulness cycles and EEG power spectra in rabbits. On the other hand, cyproheptadine (3–30 mg/kg), ketotifen (30–100 mg/kg) and PY-608 (0.3–100 mg/kg) caused increases and/or decreases of spontaneous locomotor activity, prolongation of hexobarbital-induced sleeping time and antagonistic effects on reserpine-induced hypothermia in mice. These Agents (30 mg/kg) increased slow wave sleep and enhanced EEG power spectra at low frequency bands such as δ and θ in rabbits. These findings suggest that HSR-609 has no inhibitory effect on the CNS due to its amphoteric chemical structure.

  • Studies on the novel Antiallergic Agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor.
    Japanese journal of pharmacology, 1997
    Co-Authors: Masato Kakiuchi, Tetsuo Ohashi, Kouji Morikawa, Hideo Kato, Keiichi Musoh, Kimio Kawamura
    Abstract:

    Abstract We studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5,ll-dihydro-benz[Z?]oxepino[4,3-b]pyridin-ll-ylidene)-piperidino]propionic acid dihydrate), a novel amphoteric Antiallergic Agent, on the central nervous system (CNS). Its selectivity for the histamine Hi-receptor and its ability to penetrate into the CNS were compared with those of typical Antiallergic Agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,ll-dihydro-ll-(l-methyl-4-piperidylidene)benz[b]oxepino-[4,3-b]pyridine), which has a chemical structure similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity for H1receptors in the guinea pig cerebral cortex in comparison to affinities for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while the selectivity of PY-608 for the Hi-receptor was low. The inhibitory effects of these Antiallergic Agents on histamine-induced increase of vascular permeability in mice (ED50) were compared with the displacement of [3H]mepyramine binding to H1-receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was much larger than those of cyproheptadine, ketotifen and PY-608 and larger than those of terfenadine and cetirizine. HSR-609 was found to display selective displacement of the [3H]mepyramine binding to H1receptors for lung vs cerebral cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest that HSR-609 has high selectivity for the H preceptor and poor ability to penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical structure.

  • Amphoteric drugs. 3. Synthesis and Antiallergic activity of 3-[(5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11- ylidene)piperidino]propionic acid derivatives and related compounds.
    Journal of medicinal chemistry, 1995
    Co-Authors: Nobuhiko Iwasaki, Tetsuo Ohashi, Hideo Kato, Keiichi Musoh, Yasuo Ito, Hiroyuki Nishino, Noriyuki Kado, Shingo Yasuda
    Abstract:

    An important approach to the design of Antiallergic Agents with reduced penetration into the central nervous system (CNS) is described. A series of 3-[(5,11- dihydro[1]benzoxepino[4,3-b]-pyridin-11-ylidene)piperidino]propion ic acid derivatives (31-47) and related compounds (48-54) were synthesized and evaluated for Antiallergic activity and penetration of a compound into the CNS in comparison with the corresponding 6H-dibenz[b,e]oxepin derivative (3). Combination of zwitterionization and introduction of a pyridine component resulted in an increase in Antiallergic activity and a great reduction of penetration into the CNS, which was evaluated by the selectivity (B/A) of antihistaminic activities in the central system [ID50 value (B) for ex vivo H1 binding to mouse brain membranes] and in the peripheral system [ED50 value (A) for inhibitory effect on histamine-induced increase in vascular permeability in mice]. This surprising reduction of penetration into the CNS could be considered on the basis of an increase in hydrophilicity caused by both of the zwitterionization and the introduction of a pyridine component. 3-[4-(8-Fluoro-5,11-dihydro[1]benzoxepino[4,3- b]pyridin-11-ylidene)piperidino]propionic acid (33) exhibited a strong Antiallergic effect in various experimental models and very low penetration into the CNS. Compound 33 (HSR-609) is now under clinical trial as a promising Antiallergic Agent with greatly reduced penetration into the CNS.

  • study on zwitter ionization of drugs ii synthesis and pharmacological activity of some n 3 5h dibenzo a d cyclohepten 5 ylidene propyl n methylamino and n 3 6h dibenz b e oxepin 11 ylidene propyl n methylamino alkanoic acid derivatives and related co
    Chemical & Pharmaceutical Bulletin, 1993
    Co-Authors: Hiromi Muramatsu, Masato Kakiuchi, Tetsuo Ohashi, Hideo Kato, Nobuhiko Iwasaki, Hiroyuki Sawanishi, Y Ito
    Abstract:

    A series of N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino- (6a) and N-[3-(6H-dibenz-[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic acid derivatives (6b) and related compounds (6c-f) were synthesized and examined for pharmacological activities in vitro, i.e., inhibitory effect on monoamine [noradrenaline (NA) and 5-hydroxytryptamine (5-HT)] uptake, inhibitory effect on 5-HT-, histamine-, acetylcholine- and NA-induced contraction, and binding affinity for α2-adrenoceptor and dopamine D2-receptor. In vitro tests indicated that zwitter-ionization was capable of maintaining H1-antihistaminic activity while greatly reducing other pharmacological activities. Further, 6a-f showed much stonger inhibitory effects on compound 48/80-induced lethality in rats than did the corresponding N, N-dimethylamines (2a-f). 3-[N-[3-(6H-Dibenz[b, e]oxepin-11-ylidene)propyl]-N-methylamino]-propionic acid (6b-2), selected as a candidate Antiallergic Agent of a new type, equally potent in rats and guinea-pigs, exhibited strong inhibitory effects on 48 h homologous passive cutaneous anaphylaxis (PCA) in rats (ED50=0.019 mg/kg, p.o.) and on histamine-induced bronchoconstriction in anesthetized guinea-pigs (ED50=0.0067 mg/kg, p.o.).

Masaaki Matsuo - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis and Pharmacological Properties of N‐(4‐(4‐(1H‐Indol‐3‐yl) piperidinoalkyl)‐2‐thiazolyl)alkanesulfonamides as Novel Antiallergic Agents.
    ChemInform, 2010
    Co-Authors: Shinji Shigenaga, Jun Hiroi, Takashi Fujii, Takashi Manabe, Hiroshi Matsuda, Masaaki Matsuo
    Abstract:

    A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanesulfonamides (8-21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfonamide (8, FK613) for further development as a novel Antiallergic Agent. Clinical evaluation of FK613 is now in progress.

  • Synthesis and Pharmacological Properties of N-[4-[4-(1H-Indol-3-yl)-piperidinoalkyl]-2-thiazolyl]alkanesulfonamides as Novel Antiallergic Agents
    Chemical & pharmaceutical bulletin, 1993
    Co-Authors: Shinji Shigenaga, Jun Hiroi, Takashi Fujii, Takashi Manabe, Hiroshi Matsuda, Masaaki Matsuo
    Abstract:

    A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanesulfonamides (8-21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfonamide (8, FK613) for further development as a novel Antiallergic Agent. Clinical evaluation of FK613 is now in progress.

Mi Heon Ryu - One of the best experts on this subject based on the ideXlab platform.

  • Research Article Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer
    2016
    Co-Authors: Hsc- Cells, Seung-hwa Jeong, Hyungwoo Kim, Mi Heon Ryu
    Abstract:

    Copyright © 2015 Hye-Yeon Han et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Poncirus trifoliata Rafin. has long been used as anti-inflammatory and Antiallergic Agent to treat gastrointestinal disorders and pulmonary diseases such as indigestion, constipation, chest fullness, chest pain, bronchitis, and sputum inKorea. P. trifoliata extract has recently been reported to possess anticancer properties; however, its mechanisms of action remain unclear. In this study, its antiproliferative effects and possible mechanisms were investigated in HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC) 50 = 142.

  • Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer HSC-4 Cells
    Hindawi Limited, 2015
    Co-Authors: Hye-yeon Han, Seung-hwa Jeong, Hyungwoo Kim, Mi Heon Ryu, Bong-soo Park, Guem San Lee
    Abstract:

    Poncirus trifoliata Rafin. has long been used as anti-inflammatory and Antiallergic Agent to treat gastrointestinal disorders and pulmonary diseases such as indigestion, constipation, chest fullness, chest pain, bronchitis, and sputum in Korea. P. trifoliata extract has recently been reported to possess anticancer properties; however, its mechanisms of action remain unclear. In this study, its antiproliferative effects and possible mechanisms were investigated in HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 μg/mL) in a dose-dependent manner. While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment. Furthermore, 3-methyladenine (3-MA, autophagy inhibitor) effectively blocked the MEPT-induced cytotoxicity of HSC-4 cells and triggered the activation of p38 and extracellular signal-regulated kinases (ERK) proteins. Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway