MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action

Miyoshi, Kazuhisa; Kanda, Atsuhiro; Miyake, Hidekazu; Ichihara, Kenji; Kamei, Hiroyuki; Nagasaka, Mitsuaki

doi:10.1016/0014-2999(93)90841-5

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…The rate constants for the onset of the effects of aranidipine and its metabolites on femoral blood flow were also smaller than the constant for nifedipine ( Table 2). As reported previously (Miyoshi et al 1993), nitrendipine increased femoral blood flow to a degree comparable with that of nifedipine at a lower dose (3 nmol/min), and its effect, like that of nifedipine, disappeared immediately. When the rate constant for the decay of the effect of nitrendipine was estimated, the recovery from the effect of nitrendipine on femoral blood flow was almost the same as that for nifedipine.…”

Section: Measurement Of Femoral Blood Flow In Anesthetized Dogssupporting

confidence: 59%

“…1), appreciably inhibited Ca 2+ -induced contraction in isolated rabbit arteries . They were several fold less potent than aranidipine, in agreement with their lower affinity for the dihydropyridine binding site (Miyoshi et al 1993). The hypotensive activities of these metabolites were also lower than that of aranidipine, but were comparable to that of nifedipine (Kanda et al 1992).…”

Section: Introductionmentioning

confidence: 58%

“…To elucidate the vascular actions of M-1(a) and M-1(b), anesthetized dogs were given these agents by intra-arterial infusion as previously reported (Miyoshi et al 1993). This enables the effects of the drugs on peripheral vascular beds containing resistance vessels under conditions in which the neurogenic factors were intact to be evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Femoral blood flow was measured by the procedure reported previously (Miyoshi et al 1993). In short, dogs were anesthetized with pentobarbital sodium (30 mg/kg, i.v.…”

Section: Methodsmentioning

confidence: 99%

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Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine

Miyoshi

Miyake

Ichihara

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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Aranidipine, a novel dihydropyridine derivative, gives rise to two active metabolites, M-1(alpha) and M-1(beta), which exhibit hypotensive activity comparable to that of nifedipine. The aim of this study was to examine the recovery phase of the vasodilating effect of M-1(alpha) and of M-1(beta), to determine their binding characteristics and to compare the results with those for aranidipine and other dihydropyridine derivatives. During intra-arterial infusion into the femoral vascular beds of anesthetized dogs, M-1(alpha), M-1(beta), and nifedipine, produced increases in femoral blood flow at doses three times higher than the dose of aranidipine required to produce a comparable effect. The onset and recovery of the effects of the metabolites on femoral blood flow were significantly slower than the onset and recovery of the effect of nifedipine. The inhibitory activities of M-1(alpha) and M-1(beta) towards stimulated 45Ca uptake in isolated guinea pig aorta were less than that of aranidipine. In binding studies, using porcine heart membrane preparations, [3H]M-1(alpha) and [3H]M-1(beta) had larger Kd values than [3H]aranidipine and [3H]nitrendipine, but the maximal binding number for each of them was almost the same. The association and dissociation rate constants for [3H]M-1(alpha) and [3H]M-1(beta) binding, as well as those for [3H]aranidipine binding, were significantly smaller than those for [3H]nitrendipine, corresponding to the recovery of the in vivo vasodilating effects of the metabolites. The dissociation rate constants of these radiolabeled ligands were highly positively correlated with the elimination rate constants of their in vivo vasodilating effects. From these results, we conclude that M-1(alpha) and M-1(beta), although their binding affinities and Ca2+ antagonistic actions are less potent, possess slower kinetic binding properties than many other dihydropyridines and that the slow kinetic interaction of these metabolites with the dihydropyridine receptor may contribute to the long-lasting in vivo vasodilating effect of aranidipine.

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Section: Measurement Of Femoral Blood Flow In Anesthetized Dogssupporting

confidence: 59%

Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

“…Femoral blood flow was measured by the procedure reported previously (Miyoshi et al 1993). In short, dogs were anesthetized with pentobarbital sodium (30 mg/kg, i.v.…”

Section: Methodsmentioning

confidence: 99%

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Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine

Miyoshi

Miyake

Ichihara

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Aranidipine, (B)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl) 3,5-pyridinedicarboxylate, is a novel 1,4-dihydropyridine derivative that has been shown to possess potent and long-lasting vasodilative and antihypertensive actions [1][2][3]. A remarkable characteristic of aranidipine is its high negative chronotropic potency.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of T-Type and L-Type Ca<sup>2+</sup> Currents by Aranidipine, a Novel Dihydropyridine Ca<sup>2+</sup> Antagonist

Masumiya

Tanaka²,

Tanaka³

et al. 2000

Pharmacology

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The effects of aranidipine, a novel dihydropyridine Ca²⁺ channel antagonist, on membrane currents in guinea pig ventricular myocytes and on action potentials in rabbit sinoatrial node tissue were examined. In myocytes, aranidipine (10 nmol/l to 1 μmol/l) concentration-dependently decreased T-type and L-type Ca²⁺ currents. Aranidipine (1 μmol/l) had little effect on K⁺ currents. In the sinoatrial node, 0.1 μmol/l aranidipine increased cycle length, and decreased +v̇_max and the slope of the phase 4 depolarization. Thus, inhibition of both T-type and L-type Ca²⁺ currents by aranidipine may partly explain its potent negative chronotropic activity.

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Cardiovascular Agents

Joshi

Burnett

2003

Kirk-Othmer Encyclopedia of Chemical Technology

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Cardiovascular disease still remains the nation's number one killer of men and women of all races, in spite of tremendous advances in basic and clinical research greatly helping to improve the prevention, treatment, and mortality of heart disease. It is estimated that ∼40% of Americans (∼60 million between the ages of 40–70) suffer from some degree of this disease. The problem of treating heart diseases has been at the forefront of the international medical community, and the cardiovascular drug market has been leading the drug discovery efforts in sales for the past two decades. A constant flow of new and effective drugs has kept this sector in its number one position and will continue to do so in the future. The development of unique, novel, and tissue specific cardiac drugs to replace or supplement existing therapies for various cardiac disorders continues to generate significant and growing attention. This has evolved hand‐in‐hand with research that has facilitated a better understanding of the underlying causes of cardiac disease states. The first draft of the human genome map is a turning point in the research for new medicines that will address the cause, versus the symptoms, of many human ailments including cardiovascular diseases. This article focuses on the review of past treatments, significant new developments, and future therapies for the treatment of various cardiovascular diseases. The article is divided into six sections: antiarrhythmic agents, antianginal agents, antihypertensive agents, antilipemic agents, antithrombolytic agents, and other therapeutics. Each section is further discussed in depth as per the classification of agents based upon their mechanism of action and clinical application. This article is designed primarily to serve the needs of a wide audience.

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MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action

Cited by 11 publications

References 18 publications

Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine

Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine

Inhibition of T-Type and L-Type Ca<sup>2+</sup> Currents by Aranidipine, a Novel Dihydropyridine Ca<sup>2+</sup> Antagonist

Cardiovascular Agents

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