Combined Effects of Benidipine and Diltiazem in a Rat Model of Experimental Angina

Yao, Kozo; Shirakura, Shiro

doi:10.1254/jphs.sc0030119

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…Combination effects of benidipine and diltiazem for the treatment of angina have also been reported in rats (90). Benidipine shows more vascular selectivity and less negative inotropic activity compared to diltiazem, and induces a longer-lasting increase in coronary blood flow (96,97).…”

Section: Cardioprotective Effectsmentioning

confidence: 99%

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Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

Yao

Nagashima

Miki³

2006

J Pharmacol Sci

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Abstract. Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardioprotective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects.

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Section: Cardioprotective Effectsmentioning

confidence: 99%

“…Potent antianginal effects of benidipine have been shown in various models of angina (90,91,96). Combination effects of benidipine and diltiazem for the treatment of angina have also been reported in rats (90).…”

Section: Cardioprotective Effectsmentioning

confidence: 99%

Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

Yao

Nagashima

Miki³

2006

J Pharmacol Sci

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“…Recently, we reported that the combination of diltiazem and benidipine exerted potent antianginal effects in the vasopressin-induced angina rat model. 5) To elucidate the beneficial effects of the combination of benidipine and diltiazem in angina, the present study focused on CF and DP in anesthetized dogs. The results of the present study demonstrates that the combination of benidipine and diltiazem significantly decreased DP in comparison to benidipine alone, and significantly and continuously increased CF.…”

Section: Discussionmentioning

confidence: 99%

“…We reported recently that the combination of diltiazem and benidipine exerted potent antianginal effects in the vasopressin-induced angina rat model. 5) However, there have been no published reports concerning the hemodynamic profile of the combination of diltiazem and benidipine. Therefore, in the present study we examined the hemodynamic effects of diltiazem, benidipine, and the combination of these drugs in anesthetized dogs.…”

mentioning

confidence: 99%

“…The doses of benidipine (3 mg/kg) and diltiazem (300, 1000 mg/kg) were selected on the basis of the study by Yao and Shirakura. 5) For analysis experiments, benidipine-d 5 as an internal standard (I.S., 96.3% isotopic purity) for the determination of benidipine was synthesized in the Pharmaceutical Research Center, Kyowa Hakko Kogyo. Diltiazem hydrochloride and verapamil hydrochloride as I.S.…”

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confidence: 99%

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Combined Effects of Benidipine and Diltiazem on Cardiohemodynamics in Anesthetized Dogs

Yao

Maeda

Ina

et al. 2006

Biological & Pharmaceutical Bulletin

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We examined the combined effects of the calcium channel blockers 1,4-dihydropyridine (benidipine) and benzothiazepine (diltiazem) on cardiohemodynamics in anesthetized dogs. Benidipine (3 m mg/kg) lowered blood pressure (BP) slightly and continuously increased coronary flow (CF). Diltiazem (300, 1000 m mg/kg) decreased BP, heart rate (HR), and the maximum rate of rise of left ventricular pressure (LV dP/dt max) with the increase of doses. Diltiazem increased CF, though it was transient when compared to benidipine. A combination of benidipine (3 m mg/kg) and diltiazem (300 m mg/kg) showed continuous decreases in BP, HR, and LV dP/dt max, and an increase in CF that was similar to that recorded for the benidipine group. The level of double product (DP: systolic BP؋HR, an index of myocardium energy consumption) in the combination group was significantly lower than that of the benidipine group. The plasma concentrations of benidipine and diltiazem in the combination group were similar to those of the groups receiving either drug. These results demonstrate that the combination of benidipine and diltiazem increases CF more continuously than diltiazem alone, and decreases DP more potently than benidipine alone, indicating that the combination therapy possesses favorable properties as a treatment for angina pectoris. Therefore, the combination of benidipine and diltiazem is suggested as a useful treatment for improving the clinical benefits of monotherapy for angina, compared with the use of diltiazem alone at higher doses.

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Comparison of anti-anginal effect of cilnidipine with those of nicardipine and nifedipine in the vasopressin-induced angina model of rats

et al. 2016

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We assessed the anti-anginal effects of cilnidipine in comparison with those of nicardipine and nifedipine (1 and 10 µg/kg, n = 6 for each drug) or vehicle (n = 6) by using the vasopressin-induced angina model of rats. The administration of vasopressin (0.5 IU/kg, i.v.) to the rats depressed the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it significantly increased the mean blood pressure, resulting in the decrease of the heart rate and the prolongation of the PR interval possibly through a reflex-mediated increase in vagal tone. Cilnidipine suppressed the vasopressin-induced depression of the S-wave level in a dose-related manner, which was not observed by nicardipine or nifedipine. In addition, the low dose of cilnidipine hardly affected the vasopressin-induced pressor response, but it attenuated the negative dromotropic effect, suggesting N-type Ca channel inhibition by cilnidipine might have suppressed the parasympathetic nerve activity in vivo like those reported in the sympathetic nerve. Thus, cilnidipine may become a useful strategy for inhibiting coronary vasospasm-induced anginal attack.

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Combined Effects of Benidipine and Diltiazem in a Rat Model of Experimental Angina

Cited by 9 publications

References 14 publications

Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

Combined Effects of Benidipine and Diltiazem on Cardiohemodynamics in Anesthetized Dogs

Comparison of anti-anginal effect of cilnidipine with those of nicardipine and nifedipine in the vasopressin-induced angina model of rats

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