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C Yoshida - One of the best experts on this subject based on the ideXlab platform.
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pharmacological studies on 3 formylamino 7 methylsulfonylamino 6 phenoxy 4h 1 benzopyran 4 one t 614 a novel Antiinflammatory Agent 4th communication inhibitory effect on the production of interleukin 1 and interleukin 6
Journal of pharmacobio-dynamics, 1992Co-Authors: Keiichi Tanaka, Yukihiko Aikawa, Takihiro Inaba, Hiroki Kawasaki, Keiko Asaoka, C YoshidaAbstract:In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel Antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1β from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 μg/ml). The release of IL-6 from THP-1 cells, as detrmined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC50 values of 2.0 and 6.6 μg/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1β production is caused by the suppression of IL-1β mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its Antiinflammatory activities.
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pharmacological studies of the new Antiinflammatory Agent 3 formylamino 7 methylsulfonylamino 6 phenoxy 4 1 benzopyran 4 o ne 2nd communication effect on the arachidonic acid cascades
Drug Research, 1992Co-Authors: Keiichi Tanaka, Shinji Makino, Tomoya Shimotori, Yukihiko Aikawa, Takihiro Inaba, C YoshidaAbstract:Abstract The in vitro and in vivo effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0), a new Antiinflammatory Agent, on arachidonic acid metabolism were investigated in comparison with those of reference drugs. Although the inhibitory effect of T-614 on the synthesis of prostaglandins by rabbit renal microsomes was very weak (IC50 of 58 micrograms/ml), T-614 effectively inhibited the prostaglandin E2 (PGE2) generation by mouse fibroblasts stimulated with bradykinin with an IC50 value of 0.47 micrograms/ml. The suppressive effect of T-614 on the PGE2 generation in fibroblasts was also found when cells were stimulated with Ca ionophore A23187, but not when induced with arachidonic acid. T-614 suppressed the A23187-induced PGE2 generation by rat macrophages, but not the leukotriene B4 production. In addition, 5-lipoxygenase activities in guinea-pig peritoneal exudated cells were not inhibited. In in vivo experiments, at doses of more than 1 mg/kg, T-614 reduced the PGE2 contents in inflammatory exudate of rat carrageenin-sponge type inflammation, but it was almost inactive in inhibiting gastric prostaglandins production up to 100 mg/kg. T-614 also did not affect the urinary PGE2 excretion in rats, and slightly inhibited the thromboxane synthesis in rat blood. Furthermore, the convulsion-induced increase of PGE2 in mouse brain was inhibited by T-614. These data suggest that T-614 inhibits the production of cyclooxgenase-mediated products with apparently different mode from classical non-steroidal Antiinflammatory drugs, and may partly explain the discrepancy in pharmacological properties between this compound and other drugs.
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pharmacological studies of the new Antiinflammatory Agent 3 formylamino 7 methylsulfonylamino 6 phenoxy 4h 1 benzopyran 4 o ne 1st communication Antiinflammatory analgesic and other related properties
Drug Research, 1992Co-Authors: Keiichi Tanaka, Shinji Makino, Tomoya Shimotori, Yukihiko Aikawa, Takihiro Inaba, C Yoshida, Shuntaro TakanoAbstract:The Antiinflammatory, analgesic and antipyretic activities of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614, CAS 123663-49-0) were investigated in various animal models and compared with those of nimesulide, indometacin and ibuprofen. The Antiinflammatory potency of T-614 on carrageenin-induced paw edema, paper disk granuloma and established adjuvant arthritis was greater than that of ibuprofen, but slightly lower than those of nimesulide and indometacin
Keiichi Tanaka - One of the best experts on this subject based on the ideXlab platform.
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pharmacological studies on 3 formylamino 7 methylsulfonylamino 6 phenoxy 4h 1 benzopyran 4 one t 614 a novel Antiinflammatory Agent 4th communication inhibitory effect on the production of interleukin 1 and interleukin 6
Journal of pharmacobio-dynamics, 1992Co-Authors: Keiichi Tanaka, Yukihiko Aikawa, Takihiro Inaba, Hiroki Kawasaki, Keiko Asaoka, C YoshidaAbstract:In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel Antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1β from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 μg/ml). The release of IL-6 from THP-1 cells, as detrmined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC50 values of 2.0 and 6.6 μg/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1β production is caused by the suppression of IL-1β mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its Antiinflammatory activities.
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pharmacological studies of the new Antiinflammatory Agent 3 formylamino 7 methylsulfonylamino 6 phenoxy 4 1 benzopyran 4 o ne 2nd communication effect on the arachidonic acid cascades
Drug Research, 1992Co-Authors: Keiichi Tanaka, Shinji Makino, Tomoya Shimotori, Yukihiko Aikawa, Takihiro Inaba, C YoshidaAbstract:Abstract The in vitro and in vivo effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0), a new Antiinflammatory Agent, on arachidonic acid metabolism were investigated in comparison with those of reference drugs. Although the inhibitory effect of T-614 on the synthesis of prostaglandins by rabbit renal microsomes was very weak (IC50 of 58 micrograms/ml), T-614 effectively inhibited the prostaglandin E2 (PGE2) generation by mouse fibroblasts stimulated with bradykinin with an IC50 value of 0.47 micrograms/ml. The suppressive effect of T-614 on the PGE2 generation in fibroblasts was also found when cells were stimulated with Ca ionophore A23187, but not when induced with arachidonic acid. T-614 suppressed the A23187-induced PGE2 generation by rat macrophages, but not the leukotriene B4 production. In addition, 5-lipoxygenase activities in guinea-pig peritoneal exudated cells were not inhibited. In in vivo experiments, at doses of more than 1 mg/kg, T-614 reduced the PGE2 contents in inflammatory exudate of rat carrageenin-sponge type inflammation, but it was almost inactive in inhibiting gastric prostaglandins production up to 100 mg/kg. T-614 also did not affect the urinary PGE2 excretion in rats, and slightly inhibited the thromboxane synthesis in rat blood. Furthermore, the convulsion-induced increase of PGE2 in mouse brain was inhibited by T-614. These data suggest that T-614 inhibits the production of cyclooxgenase-mediated products with apparently different mode from classical non-steroidal Antiinflammatory drugs, and may partly explain the discrepancy in pharmacological properties between this compound and other drugs.
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pharmacological studies of the new Antiinflammatory Agent 3 formylamino 7 methylsulfonylamino 6 phenoxy 4h 1 benzopyran 4 o ne 1st communication Antiinflammatory analgesic and other related properties
Drug Research, 1992Co-Authors: Keiichi Tanaka, Shinji Makino, Tomoya Shimotori, Yukihiko Aikawa, Takihiro Inaba, C Yoshida, Shuntaro TakanoAbstract:The Antiinflammatory, analgesic and antipyretic activities of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614, CAS 123663-49-0) were investigated in various animal models and compared with those of nimesulide, indometacin and ibuprofen. The Antiinflammatory potency of T-614 on carrageenin-induced paw edema, paper disk granuloma and established adjuvant arthritis was greater than that of ibuprofen, but slightly lower than those of nimesulide and indometacin
Sumner Burstein - One of the best experts on this subject based on the ideXlab platform.
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Dimethylheptyl‐THC‐11 OIC acid: A nonpsychoactive Antiinflammatory Agent with a cannabinoid template structure
Arthritis & Rheumatism, 1998Co-Authors: Robert B Zurier, Ronald G Rossetti, Joan H Lane, John M Goldberg, Sheila A Hunter, Sumner BursteinAbstract:Objective To assess the Antiinflammatory activity of dimethylheptyl-THC-11 oic acid (DMH-11C), a nonpsychoactive synthetic derivative of tetrahydrocannabinol. Methods Acute inflammation was induced by injection of interleukin-1β and tumor necrosis factor α into subcutaneous air pouches formed on the backs of mice. Inflammation was quantified 6 hours later by pouch fluid leukocyte counts. Adjuvant-induced polyarthritis in rats was used as a model of chronic inflammation and joint tissue injury. Animals were either untreated, treated with safflower oil, or treated with DMH-11C in safflower oil. Arthritis was assessed by clinical observation and by histomorphologic evaluation of tibiotarsal joints. Results Oral administration of DMH-11C reduced the accumulation of pouch fluid leukocytes and significantly reduced the severity of adjuvant-induced polyarthritis. Histopathologic studies of tibiotarsal joints showed that DMH-11C treatment attenuated pannus formation and joint tissue injury. Conclusion DMH-11C suppresses acute inflammation in the subcutaneous air pouch in mice and chronic joint inflammation characteristic of adjuvant disease in rats. These results demonstrate the potential use of this nonpsychoactive cannabinoid as an Antiinflammatory Agent.
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dimethylheptyl thc 11 oic acid a nonpsychoactive Antiinflammatory Agent with a cannabinoid template structure
Arthritis & Rheumatism, 1998Co-Authors: Robert B Zurier, Ronald G Rossetti, Joan H Lane, John M Goldberg, Sheila A Hunter, Sumner BursteinAbstract:Objective To assess the Antiinflammatory activity of dimethylheptyl-THC-11 oic acid (DMH-11C), a nonpsychoactive synthetic derivative of tetrahydrocannabinol. Methods Acute inflammation was induced by injection of interleukin-1β and tumor necrosis factor α into subcutaneous air pouches formed on the backs of mice. Inflammation was quantified 6 hours later by pouch fluid leukocyte counts. Adjuvant-induced polyarthritis in rats was used as a model of chronic inflammation and joint tissue injury. Animals were either untreated, treated with safflower oil, or treated with DMH-11C in safflower oil. Arthritis was assessed by clinical observation and by histomorphologic evaluation of tibiotarsal joints. Results Oral administration of DMH-11C reduced the accumulation of pouch fluid leukocytes and significantly reduced the severity of adjuvant-induced polyarthritis. Histopathologic studies of tibiotarsal joints showed that DMH-11C treatment attenuated pannus formation and joint tissue injury. Conclusion DMH-11C suppresses acute inflammation in the subcutaneous air pouch in mice and chronic joint inflammation characteristic of adjuvant disease in rats. These results demonstrate the potential use of this nonpsychoactive cannabinoid as an Antiinflammatory Agent.
Csaba Szabo - One of the best experts on this subject based on the ideXlab platform.
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Collagen induced arthritis: Reversal by mercaptoethylguanidine, a novel Antiinflammatory Agent with a combined mechanism of action
The Journal of Rheumatology, 1998Co-Authors: Ernest Brahn, Mona Lisa Banquerigo, Gary S. Firestein, David L. Boyle, Andrew L. Salzman, Csaba SzaboAbstract:Objective, We recently identified mercaptoethylguanidine (MEG) as an Antiinflammatory Agent with a combined mechanism of action. Its effects include inhibition of the inducible isoform of nitric oxide synthase (iNOS), scavenging peroxynitrite, a cytotoxic oxidant species produced from nitric oxide (NO) and superoxide, and inhibition of cyclooxygenase (COX). We investigate the effect of MEG in collagen induced arthritis (CIA). Methods. Syngeneic LOU rats were immunized with native type II collagen on Day 0. After clinical signs of arthritis developed on Day 10, treatment with MEG was initiated (30 mg/kg ip tid) and continued until sacrifice on Day 28. Serum nitrite/nitrate was measured in control animals, at arthritis onset and 2 days after the start of MEG treatment. Clinical scores were obtained daily. At Day 28, radiographic scores were obtained, and joints were harvested for the measurement of mRNA for tumor necrosis factor-α (TNF-α), collagenase, and stromelysin. Results. Serum nitrite/nitrate increased from 7.9 ± 0.7 mM (baseline) to 13.5 ±2.6 at arthritis onset (p
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collagen induced arthritis reversal by mercaptoethylguanidine a novel Antiinflammatory Agent with a combined mechanism of action
The Journal of Rheumatology, 1998Co-Authors: Ernest Brahn, Mona Lisa Banquerigo, Gary S. Firestein, David L. Boyle, Andrew L. Salzman, Csaba SzaboAbstract:Objective, We recently identified mercaptoethylguanidine (MEG) as an Antiinflammatory Agent with a combined mechanism of action. Its effects include inhibition of the inducible isoform of nitric oxide synthase (iNOS), scavenging peroxynitrite, a cytotoxic oxidant species produced from nitric oxide (NO) and superoxide, and inhibition of cyclooxygenase (COX). We investigate the effect of MEG in collagen induced arthritis (CIA). Methods. Syngeneic LOU rats were immunized with native type II collagen on Day 0. After clinical signs of arthritis developed on Day 10, treatment with MEG was initiated (30 mg/kg ip tid) and continued until sacrifice on Day 28. Serum nitrite/nitrate was measured in control animals, at arthritis onset and 2 days after the start of MEG treatment. Clinical scores were obtained daily. At Day 28, radiographic scores were obtained, and joints were harvested for the measurement of mRNA for tumor necrosis factor-α (TNF-α), collagenase, and stromelysin. Results. Serum nitrite/nitrate increased from 7.9 ± 0.7 mM (baseline) to 13.5 ±2.6 at arthritis onset (p <0.05). Within 48 h of MEG treatment, nitrite/nitrate levels fell to 7.2 ±1.1 (p<0.05). By Day 28, clinical arthritis scores (measured on a scale of 0-8) were 7.1 ± 0.6 in the vehicle group compared to 1.4± 0.6 in the MEG treated group (p <0.0001). Radiographic scores (scale 0-6) on Day 28 were reduced from 4.9±0.6 to 0.6± 0.4 (p < 0.0002) by MEG treatment. MEG reduced the synovial expression of mRNA for TNF-α, collagenase, and stromelysin by 72, 67, and 52%, respectively. Conclusion. These data show that MEG has beneficial effects on established CIA. The mechanism of action may be related to inhibition of synovial iNOS expression or activity, inhibition of COX, scavenging of peroxynitrite, with subsequent inhibition of angiogenesis, metalloproteinase, and TNF-α expression.
Takihiro Inaba - One of the best experts on this subject based on the ideXlab platform.
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pharmacological studies on 3 formylamino 7 methylsulfonylamino 6 phenoxy 4h 1 benzopyran 4 one t 614 a novel Antiinflammatory Agent 4th communication inhibitory effect on the production of interleukin 1 and interleukin 6
Journal of pharmacobio-dynamics, 1992Co-Authors: Keiichi Tanaka, Yukihiko Aikawa, Takihiro Inaba, Hiroki Kawasaki, Keiko Asaoka, C YoshidaAbstract:In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel Antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1β from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 μg/ml). The release of IL-6 from THP-1 cells, as detrmined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC50 values of 2.0 and 6.6 μg/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1β production is caused by the suppression of IL-1β mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its Antiinflammatory activities.
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pharmacological studies of the new Antiinflammatory Agent 3 formylamino 7 methylsulfonylamino 6 phenoxy 4 1 benzopyran 4 o ne 2nd communication effect on the arachidonic acid cascades
Drug Research, 1992Co-Authors: Keiichi Tanaka, Shinji Makino, Tomoya Shimotori, Yukihiko Aikawa, Takihiro Inaba, C YoshidaAbstract:Abstract The in vitro and in vivo effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0), a new Antiinflammatory Agent, on arachidonic acid metabolism were investigated in comparison with those of reference drugs. Although the inhibitory effect of T-614 on the synthesis of prostaglandins by rabbit renal microsomes was very weak (IC50 of 58 micrograms/ml), T-614 effectively inhibited the prostaglandin E2 (PGE2) generation by mouse fibroblasts stimulated with bradykinin with an IC50 value of 0.47 micrograms/ml. The suppressive effect of T-614 on the PGE2 generation in fibroblasts was also found when cells were stimulated with Ca ionophore A23187, but not when induced with arachidonic acid. T-614 suppressed the A23187-induced PGE2 generation by rat macrophages, but not the leukotriene B4 production. In addition, 5-lipoxygenase activities in guinea-pig peritoneal exudated cells were not inhibited. In in vivo experiments, at doses of more than 1 mg/kg, T-614 reduced the PGE2 contents in inflammatory exudate of rat carrageenin-sponge type inflammation, but it was almost inactive in inhibiting gastric prostaglandins production up to 100 mg/kg. T-614 also did not affect the urinary PGE2 excretion in rats, and slightly inhibited the thromboxane synthesis in rat blood. Furthermore, the convulsion-induced increase of PGE2 in mouse brain was inhibited by T-614. These data suggest that T-614 inhibits the production of cyclooxgenase-mediated products with apparently different mode from classical non-steroidal Antiinflammatory drugs, and may partly explain the discrepancy in pharmacological properties between this compound and other drugs.
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pharmacological studies of the new Antiinflammatory Agent 3 formylamino 7 methylsulfonylamino 6 phenoxy 4h 1 benzopyran 4 o ne 1st communication Antiinflammatory analgesic and other related properties
Drug Research, 1992Co-Authors: Keiichi Tanaka, Shinji Makino, Tomoya Shimotori, Yukihiko Aikawa, Takihiro Inaba, C Yoshida, Shuntaro TakanoAbstract:The Antiinflammatory, analgesic and antipyretic activities of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614, CAS 123663-49-0) were investigated in various animal models and compared with those of nimesulide, indometacin and ibuprofen. The Antiinflammatory potency of T-614 on carrageenin-induced paw edema, paper disk granuloma and established adjuvant arthritis was greater than that of ibuprofen, but slightly lower than those of nimesulide and indometacin
