Hypotensive Effects of YM430, a 1,4-Dihydropyridine Derivative, in Spontaneously Hypertensive Rats and Renal Hypertensive Dogs.

DOI Web Site PubMed 参考文献24件
  • Shibasaki Kumiko
    Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
  • Takizawa Kenji
    Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
  • Uchida Wataru
    Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
  • Takenaka Toichi
    Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

書誌事項

タイトル別名
  • Hypotensive Effects of YM430 a 1 4 Dihy

この論文をさがす

抄録

The hypotensive effects of YM430 (4(((S)-2-hydroxy-3-phenoxypropyl)amino)butyl methyl 2, 6-dimethyl-((S)-4-(m-nitrophenyl))-1, 4-dihydropyridine-3, 5-dicarboxylate)were evaluated in hypertensive animals. In conscious spontaneously hypertensive rats (SHR), single oral administration of YM430 (10-100 mg/kg)produced a dose-dependent decrease in mean blood pressure (MBP)with slight reflex tachycardia. The hypotensive effect of YM430 reached its maximum about 2 hr after dosing and lasted for over 10 hr. Importantly, the β1-adrenoceptor blocking activity of YM430 had a similar time course to that of its calcium entry blocking activity. In conscious normotensive dogs (NTD: 1-10 mg/kg, p.o.), YM430 decreased MBP without reflex tachycardia, and inhibited isoproterenol (ISO)-induced tachycardia in a dose-dependent manner. In conscious renal hypertensive dogs (RHD: 0.3-3 mg/kg, p.o.), YM430 also produced a sustained hypotensive effect. Furthermore, on repeated oral administration to conscious SHR and NTD, YM430 caused a long-lasting hypotensive effect. This hypotensive activity and inhibition of ISO-induced tachycardia showed neither tolerance, augmentation nor rebound. In conclusion, YM430 has a long-lasting hypotensive effect and behaves as a hybrid compound, combining calcium entry blocking and β1-adrenoceptor blocking activities in vivo. In addition, the degree of the blocking activities of YM430 remains nearly constant in the long-term after oral administration.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 73 (2), 113-124, 1997

    公益社団法人 日本薬理学会

参考文献 (24)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ