Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 343, Issue 4, pp 405–410 | Cite as

Mechanisms underlying the slow onset of action of a new dihydropyridine, NZ-105, on a cultured smooth muscle cell line

  • Tetsutaro Tamura
  • Akihiro Saigusa
  • Shinichiro Kokubun


The inhibitory effect of a new dihydropyridine derivative, (±)-2-[benzyl(phenyl)amino]ethyl-1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride (NZ-105), on whole cell Ca2+ current (ICa) in cultured vascular smooth muscle cells was investigated with the patch clamp technique. NZ-105 blocked ICa in a concentration-dependent manner when the command pulse ranged from +10 mV to −50 mV. The inhibitory effect of NZ-105 appeared at concentrations higher than 10 μmol/l and it blocked ICa completely at a concentration of 1 nmol/l. The concentration which produced the half-maximal inhibitory effect was estimated to be around 20 μmol/l. NZ-105 (500 pmol/l) completely blocked ICa elicited by depolarization to + 10 mV at a holding potential of −40 mV, whereas it blocked ICa by only 67% at a holding potential of −90 mV. NZ-105 (100 μmol/l) shifted the steady-state inactivation curve by 40 mV to more negative potentials without affecting its slope factor. The blocking time constant of 500 μmol/l NZ-105 was 57.6 + 9.9 s at a holding potential of −70 mV. These results indicate that NZ-105 has characteristics typical of dihydropyridines and binds to Ca2+ channels of vascular smooth muscle cells with a high affinity. They also suggested that the slow onset of its action is due to the slow binding of the drug to Ca2+ channels.

Key words

Ca2+ channel Ca2+ channel blocker Ca2+ current Slow onset of drug action Smooth muscle cell 


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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Tetsutaro Tamura
    • 1
  • Akihiro Saigusa
    • 1
  • Shinichiro Kokubun
    • 1
  1. 1.Department of PhysiologyJikei University, School of MedicineMinato-ku, TokyoJapan

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