Antiplatelet and Antithrombotic Effects of a Novel Selective Phosphodiesterase 3 Inhibitor, NSP-513, in Mice and Rats

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We investigated the effects of NSP-513, (R)-4, 5-dihydro-5-methyl-6-[4-(2-propyl-3-oxo-1-cyclo-hexenyl)amino]phenyl-3(2H)-pyridazinone, on phosphodiesterase(PDE)isozyme activities, in vitro platelet aggregation and in vivo thrombus formation.NSP-513 selectively inhibited human platelet PDE 3 isozyme with an IC<SUB>50</SUB> value of 0.039μM.In an in vitro human platelet aggregation assay, the IC<SUB>50</SUB> values(μM)of NSP-513 for platelet aggregation induced by collagen, U-46619, arachidonic acid, adenosine diphosphate(ADP), epinephrine and thrombin were 0.31, 0.25, 0.082, 0.66, 0.23 and 0.73, respectively.In a mouse pulmonary thromboembolism model, orally administered NSP-513 showed in vivo antithrombotic effects that were 320 to 470 times more potent than those of cilostazol.In a rat carotid arterial thrombosis model, intraduodenally administered NSP-513(0.1mg/kg), cilostazol(30mg/kg)and aspirin(30mg/kg)reduced thrombus formation by 75%, 66% and 48%, respectively.However, intravenously administered dipyridamole(10mg/kg)did not significantly prevent thrombus formation.These results demonstrate that NSP-513 has the potential to prevent not only in vitro platelet aggregation but also in vivo thrombus formation and indicate that the highly selective PDE 3 inhibitory effect of NSP-513 may make this compound useful for assessing the physiological role of PDE 3.

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  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 82(3), 188-198, 2000-03-01

    公益社団法人 日本薬理学会

参考文献:  38件中 1-38件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008183384
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5320975
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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