Spasmolytic effect of efonidipine hydrochloride in isolated canine coronary artery: comparison with the effects of nifedipine and nisoldipine

Biol Pharm Bull. 1997 Feb;20(2):196-200. doi: 10.1248/bpb.20.196.

Abstract

Spasmolytic effects of efonidipine hydrochloride (efonidipine) on high K(+)-, U46619- and 3,4-diaminopyridine (3,4-DAP)-induced contractions were evaluated in isolated canine coronary, artery, and were compared with the effects of nifedipine and nisoldipine. Efonidipine (0.3-30 nM), nifedipine (1-300 nM) and nisoldipine (0.1-100 nM) each relaxed the contractions induced by high K+ and U46619. However, relaxation produced by efonidipine was slower than that produced by nifedipine or nisoldipine. The rank order of potency of these drugs for U46619-induced contraction was efonidipine > or = nisoldipine > nifedipine, whereas in high K(+)-induced contraction, it was nisoldipine > efonidipine > nifedipine. Thus, the relaxing effect of efonidipine on U46619-induced contraction appeared to be more potent than its effect on high K(+)-induced contractions, when compared with the effects of nifedipine and nisoldipine. These three drugs also suppressed 3,4-DAP-induced rhythmic contractions. However, a marked time-dependent increase in potency was only observed for efonidipine, and was similar to its time-dependent effect on high K(+)- and U46619-induced contractions. Efonidipine did not change the contraction cycle length whilst suppressing the peak contractions. On the other hand, lower concentration of nifedipine at 3 nM and nisoldipine at 1 nM significantly shortened the cycle length. These results suggest that efonidipine may be an effective agent for the treatment of angina pectoris. The high potency of efonidipine for U46619-induced contractions will provide some advantages in the clinical use of this compound on thromboxane A2-mediated coronary vasoconstriction.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • 4-Aminopyridine / analogs & derivatives
  • 4-Aminopyridine / pharmacology
  • Amifampridine
  • Animals
  • Arteries / drug effects*
  • Arteries / physiology
  • Calcium Channel Blockers / pharmacology*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology
  • Dihydropyridines / pharmacology*
  • Dogs
  • In Vitro Techniques
  • Nitrophenols*
  • Organophosphorus Compounds / pharmacology*
  • Potassium / pharmacology
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Calcium Channel Blockers
  • Dihydropyridines
  • Nitrophenols
  • Organophosphorus Compounds
  • Prostaglandin Endoperoxides, Synthetic
  • Vasoconstrictor Agents
  • efonidipine
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • 4-Aminopyridine
  • Amifampridine
  • Potassium