Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. 4 Mode of action on anti-inflammatory activity.

スポンサーリンク

概要

• 論文の詳細を見る

• The possible mechanism of the anti-inflammatory activity of proglumetacin maleate (PGM), a new indomethacin (IND) derivative interacting with arachidonic acid (AA) metabolism, was investigated to elucidate the contributions of PGM itself and its two major metabolites, desproglumideproglumetacin maleate (DPP) and IND. PGM caused much less inhibition of PGE<SUB>2</SUB> formation by sheep seminal vesicle microsomes (IC50=310 μM) and TXB<SUB>2</SUB> formation by a washed rabbit platelet suspension (IC50=6.3 μM) than IND. DPP also caused less inhibition of cyclooxygenase than IND. Moreover, PGM had less effect on sodium arachidonate (SAA)-induced rat platelet aggregation ex vivo and AA-induced sudden death in rabbits than IND. These results show that PGM has anti-inflammatory activity after its conversion to the active metabolite IND. However, the inhibitory effects of PGM and DPP were as strong as that of IND on SAA- or collageninduced rabbit platelet aggregation in vitro. These activities are considered to be associated with platelet membrane interaction. Moreover, unlike IND, PGM (IC50=1.5 μM) and DPP (IC50=16.3 μM) strongly inhibited 5-HETE formation by the cytosol of guinea pig polymorphonuclear leukocytes. This unique activity of PGM on 5-lipoxygenase may contribute to its anti-inflammatory activity.

• 公益社団法人 日本薬理学会の論文

著者

• Miyake Hidekazu

  Pharmacobioregulation Research Laboratory Taiho Pharmaceutical Co. Ltd.

• MIYAKE Hidekazu

  Pharmacological Laboratory, Research Institute, Taiho Pharmaceutical Co., Ltd.

• ONO Naohiko

  Pharmacological Laboratory, Research Institute, Taiho Pharmaceutical Co., Ltd.

• YAMASAKI Yasundo

  Pharmacological Laboratory, Research Institute, Taiho Pharmaceutical Co., Ltd.

• YAMAMOTO Noriyuki

  Pharmacological Laboratory, Research Institute, Taiho Pharmaceutical Co., Ltd.

• SUNAMI Akihiko

  Pharmacological Laboratory, Research Institute, Taiho Pharmaceutical Co., Ltd.

関連論文

• Cell Type-Dependent Divergence of Transactivation by Glucocorticlid Receptor Ligand
• In Vivo Analysis of Glucocorticoid-Induced Reporter Gene Expression Using Gene Gun DNA Delivery
• Effects of MET-88,a γ-Butyrobetaine Hydroxylase Inhibitor, on Tissue Carnitine and Lipid Levels in Rats
• Realization of Cu(111) Single-Oriented State on SiO_2 by Annealing Cu-Zr Film and the Thermal Stability of Cu-Zr/ZrN/Zr/Si Contact System
• Preparation of a Contact System with a Single-Oriented (111)Al Overlayer by Interposing a Thin ZrN/Zr Bilayered Barrier Applicable to Sub-0.25-μm Design Rule
• Single-Oriented Growth of(111)Cu Film on Thin ZrN/Zr Bilayered Film for ULSI Metallization
• Study on Preparation Conditions of Single-Oriented(002)Zr Thin Films on n-(001)Si
• Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. 4 Mode of action on anti-inflammatory activity.

スポンサーリンク