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

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.

• Authors: H Jin, R Sato, R Higashino, Y Fukuda, T Kurimoto, H Tamaki
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 20 Issue 2 Pg. 196-200 (Feb 1997) ISSN: 0918-6158 [Print] Japan
• PMID: 9057986 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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