Effects of benidipine in a rat model for experimental angina.

To compare the antianginal effects of 1,4-dihydropyridine-type calcium-channel blockers, we evaluated the effects of benidipine, amlodipine, nifedipine, and efonidipine on vasopressin-induced myocardial ischemia in rats, an experimental model of angina. Intravenous administration of benidipine (3 microg/kg), amlodipine (1000 microg/kg), and nifedipine (100 microg/kg) suppressed the vasopressin-induced S-wave depression, an index of myocardial ischemia. Efonidipine (100 microg/kg, i.v.) tended to inhibit the S-wave depression. At the antianginal dose of each drug, amlodipine, nifedipine, and efonidipine decreased blood pressure significantly, whereas benidipine had little effect on blood pressure at a dose of 3 microg/kg. These results indicate that benidipine, unlike the other 1,4-dihydropyridine-type calcium-channel blockers examined in this study, inhibits vasopressin-induced coronary vasospasm with fewer undesirable effects such as hypotension in rats, suggesting that benidipine may be useful in the treatment of angina pectoris.

[1]  Kozo Yao,et al.  Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. , 2006, Journal of pharmacological sciences.

[2]  T. Moriyama,et al.  The N- and L-Type Calcium Channel Blocker Cilnidipine Suppresses Renal Injury in Dahl Rats Fed a High-Sucrose Diet, an Experimental Model of Metabolic Syndrome , 2005, Nephron Physiology.

[3]  K. Shigenobu,et al.  Pathophysiological significance of T-type Ca2+ channels: T-type Ca2+ channels and drug development. , 2005, Journal of pharmacological sciences.

[4]  H. Shimokawa,et al.  Changing Characteristics of Patients with Vasospastic Angina in the Era of New Calcium Channel Blockers , 2004, Journal of cardiovascular pharmacology.

[5]  M. Pfaffendorf,et al.  The evaluation of the N‐type channel blocking properties of cilnidipine and other voltage‐dependent calcium antagonists , 2004, Fundamental & clinical pharmacology.

[6]  K. Yao,et al.  Combined effects of benidipine and diltiazem in a rat model of experimental angina. , 2004, Journal of pharmacological sciences.

[7]  S. Yamamoto,et al.  Effect of SMP-300, a new Na+/H+ exchange inhibitor, on myocardial ischemia and experimental angina models in rats. , 2000, Japanese journal of pharmacology.

[8]  M. Shirotani,et al.  Effects of amlodipine and cilnidipine on cardiac sympathetic nervous system and neurohormonal status in essential hypertension. , 1999, Hypertension.

[9]  Y. Hirata,et al.  Effect of JTV-506, a novel vasodilator, on experimental angina model in rats. , 1998, Journal of cardiovascular pharmacology.

[10]  T. Shibano,et al.  Pharmacological profile of semotiadil fumarate, a novel calcium antagonist, in rat experimental angina model , 1995, British journal of pharmacology.

[11]  A. Karasawa,et al.  Cardiovascular effects of benidipine and amlodipine in isolated tissues and anesthetized dogs. , 1994, Biological & pharmaceutical bulletin.

[12]  W. Little,et al.  Comparison of effects of dihydropyridine calcium antagonists on left ventricular systolic and diastolic performance. , 1994, The Journal of pharmacology and experimental therapeutics.

[13]  Michael V. Green,et al.  Coronary Vasoconstriction Induced by Vasopressin: Production of Myocardial Ischemia in Dogs by Constriction of Nondiseased Small Vessels , 1991, Circulation.

[14]  K. Kubo,et al.  Calcium antagonistic effects and the in vitro duration of actions of KW-3049, a new 1,4-dihydropyridine derivative, in isolated canine coronary arteries. , 1988, Japanese journal of pharmacology.