The Potent Inhibition of Vapiprost, a Novel Thromoboxane A_2 Receptor Antagonist, on the Secondary Aggregation and ATP Release of Human Platelets

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概要

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• The inhibitory effects of vapiprost hydrochloride (vapiprost), a novel thromboxane A_2 receptor antagonist, on platelet aggregation and ATP release were studied using platelet rich plasma (PRP) of humans, guinea pigs, rabbits and rats. In in vitro experiments with human platelet, vapiprost inhibited the aggregation and ATP release stimulated with U-46619,collagen or arachidonic acid (AA) at an IC_<50> of less than 2.1×10^<-8>M. Vapiprost did not inhibit the primary aggregation or ATP release of human platelets stimulated with adenosine 5'-diphosphate (ADP), epinephrine (Epi) or platelet activating factor (PAF), but inhibited the secondary aggregation stimulated with those agonists at an IC_<50> of less than 1.3×10^<-7>M. The sensitivity of platelets in various species of animals to vapiprost was in the following order : human>guinea pigs>rats>rabbits. In ex vivo experiments with guinea pigs which received a single oral dose of vapiprost, the agent demonstrated strong inhibition of ATP release from platelets stimulated with U-46619,collagen or AA at an ID_<50> of less than 25.8 μg/kg. These inhibitory effects were observed within 30 min and sustained for 24 h at a single dosage of 5 mg/kg of vapiprost. In AA-induced pulmonary infarction models of mice, the sudden death rates decreased significantly with the oral administration of 10 mg/kg or more of vapiprost.These results indicate that vapiprost effectively inhibits the secondary aggregation and ATP release of human platelets stimulated with various agonists, and that guinea pig and human platelets are similar in response to vapiprost. Furthermore, it was demonstrated in ex vivo experiments with guinea pigs that the inhibitory action of vapiprost appears rapidly and lasts for long periods.

• 公益社団法人日本薬学会の論文
• 1997-06-15

著者

• HORIE Shuichi

  Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University

• 佐藤 公道

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kyoto University

• Satoh M

  Department Of Biochemistry Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaido

• Kurusu Osamu

  Pharmacology Group Preclinical Research Center Tsukuba Research Laboratories Nippon Glaxo Ltd.

• Horie Shuichi

  Department Of Clinical Biochemistry Faculty Of Pharmaceutical Sciences Teikyo University

• KIZAKI Keiichiro

  Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato U

• ISHII Hidemi

  Department of Pubilc Health, Faculty of Pharmaceutical Sciences

• YAMADA Mayumi

  Pharmacology Group, Preclinical Research Center, Tsukuba Research Laboratories, Nippon Glaxo Ltd.,

• SATOH Megumi

  Pharmacology Group, Preclinical Research Center, Tsukuba Research Laboratories, Nippon Glaxo Ltd.,

• NORITAKE Shinobu

  Pharmacology Group, Preclinical Research Center, Tsukuba Research Laboratories, Nippon Glaxo Ltd.,

• HIRAISHI Sayuri

  Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University

• NAKAHARA Tamio

  Pharmacology Group, Preclinical Research Center, Tsukuba Research Laboratories, Nippon Glaxo Ltd.,

• KAZAMA Mutsuyoshi

  Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University

• Ishii Hidemi

  Department Of Clinical Biochemistry Faculty Of Pharmaceutical Sciences Teikyo University

• Nakahara T

  Pharmacology Group Preclinical Research Center Tsukuba Research Laboratories Nippon Glaxo Ltd.

• Hiraishi Sayuri

  Department Of Clinical Biochemistry Faculty Of Pharmaceutical Sciences Teikyo University

• Noritake Shinobu

  Pharmacology Group Preclinical Research Center Tsukuba Research Laboratories Nippon Glaxo Ltd.

• Kizaki Keiichiro

  Department Of Clinical Biochemistry Faculty Of Pharmaceutical Sciences Teikyo University

• Kazama M

  Department Of Clinical Biochemistry Faculty Of Pharmaceutical Sciences Teikyo University

• Yamada Mayumi

  Pharmacology Group Preclinical Research Center Tsukuba Research Laboratories Nippon Glaxo Ltd.

• NAKAHARA Tamio

  Pharmaceutical Sciences, Fukuoka University

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