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

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Author(s)

Abstract

The hypotensive effects of YM430 (4(((<I>S</I>)-2-hydroxy-3-phenoxypropyl)amino)butyl methyl 2, 6-dimethyl-((<I>S</I>)-4-(<I>m</I>-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 β<SUB>1</SUB>-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 β<SUB>1</SUB>-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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 73(2), 113-124, 1997-02-01

    The Japanese Pharmacological Society

References:  24

Codes

  • NII Article ID (NAID)
    10008677060
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4153686
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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