In Vivo Pharmacologic Profile of ONO-1078: A Potent, Selective and Orally Active Peptide Leukotriene (LT) Antagonist.

スポンサーリンク

概要

• 論文の詳細を見る

• We investigated the in vivo antagonistic activity of ONO-1078 against peptide leukotrienes (LTs) in guinea pigs. ONO-1078, when administered p.o. (0.3-3 mg/kg), caused a dose-dependent reduction of LTC<SUB>4</SUB>-, LTD<SUB>4</SUB>- and LTE<SUB>4</SUB>-induced bronchoconstriction, LTD<SUB>4</SUB>-induced airway microvascular leakage and LTD<SUB>4</SUB>-induced increase in cutaneous vascular permeability. When administered intravenously, ONO-1078 (3-30 μg/kg) inhibited these responses approximately 200-600 fold more potently than FPL55712. When guinea pigs were treated with indomethacin to examine the antagonism of ONO-1078 on the direct action against peptide LTs, intravenous (3-30 μg/kg) and oral (0.3-3 mg/kg) administration of ONO-1078 also inhibited LTC<SUB>4</SUB>- and LTD<SUB>4</SUB>-induced bronchoconstriction, and its activity was approximately 300-500 fold more potent than that of FPL55712. ONO-1078 (10 mg/kg, i.v.) had no inhibitory effect on bronchoconstrictions induced by histamine, acetylcholine, serotonin, arachidonic acid, LTB<SUB>4</SUB>, prostaglandin (PG) F<SUB>2α</SUB>, PGD<SUB>2</SUB>, 9α, 11β-PGF<SUB>2</SUB>, a stable thromboxane A<SUB>2</SUB> mimetic agent and platelet activating factor. Furthermore, oral administration of ONO-1078 (1-10 mg/kg) inhibited slow-reacting substance of anaphylaxis mediated bronchoconstriction induced by antigen in a dose-dependent manner. These results indicate that ONO-1078 is an extremely potent, selective and orally active peptide LT antagonist and that oral administration of ONO-1078 antagonizes not only exogenously administered peptide LTs but also endogenous peptide LTs.

• 公益社団法人 日本薬理学会の論文

著者

• Nakagawa Naoki

  Minase Research Institute Ono Pharmaceutical Co. Ltd.

• OBATA Takaaki

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

• Aishita Hideki

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

• Nambu Fumio

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

• Kobayashi Tadamasa

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

• Okada Yutaka

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

• Terawaki Tamiya

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

関連論文

• Discovery of New Orally Active Phosphodiesterase (PDE4) Inhibitors
• Cysteinyl Leukotrienes Induce Nasal Symptoms of Allergic Rhinitis via a Receptor-Mediated Mechanism in Guinea Pigs
• Effects of a Specific Cysteinyl Leukotriene Antagonit, Pranlukast, on Antigen-Induced Cysteinyl Leukotriene-Mediated Rhinitis in Guinea Pigs
• Inhibitory Effect of OP-41483.ALPHA.-CD, a Prostacyclin Analog, on Peripheral Vascular Lesion Models in Rats.
• In Vivo Pharmacologic Profile of ONO-1078: A Potent, Selective and Orally Active Peptide Leukotriene (LT) Antagonist.
• In Vitro Antagonism of ONO-1078, a Newly Developed Anti-Asthma Agent, against Peptide Leukotrienes in Isolated Guinea Pig Tissues.
• Inhibitory effects of OKY-046 on spasmogen-induced bronchoconstrictions in sensitized and non-sensitized guinea pigs.

スポンサーリンク