Effects of disopyramide on SA nodal pacemaker activity and contractility in the isolated blood-perfused atrium of the dog

Chiba, Shigetoshi; Kobayashi, Miyoharu; Furukawa, Yoshiko

doi:10.1016/0014-2999(79)90098-0

Cited by 9 publications

(4 citation statements)

References 15 publications

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“…10B). Discussion The present study using the blood-perfused isolated preparations revealed effects of pir menol and disopyramide in arterial blood and provided new information about their direct or indirect effects on cardiac properties, which has not been reported except for the data on disopyramide by Chiba and co-workers (16,17) using the SA node preparation and those by Satoh et al (13) using the AV node prep aration. Pirmenol injected directly into the in vitro preparations showed negative chrono tropic and inotropic effects, which were com parable to those of disopyramide.…”

Section: Effects Of Disopyramidementioning

confidence: 52%

Comparison of Cardiovascular Effects of Pirmenol with Those of Disopyramide in Isolated Canine Heart Preparations Cross-Circulated with a Donor Dog

Sugiyama

Motomura²,

Tamura

et al. 1990

Japanese Journal of Pharmacology

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Abstract-To assess the cardiovascular profiles of pirmenol, a new antiarrhythmic drug, and to compare them with those of disopyramide, isolated canine sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. Pirmenol injected intraarterially into the isolated prep arations showed negative chronotropic and inotropic effects, which were com parable to those of disopyramide;and it also showed coronary vasodilator and negative dromotropic effects on atrio-His as well as His-ventricular conduction, which were significantly more potent than those of disopyramide. Similarly, pirmenol administered intravenously into the donor dog showed more potent negative dromotropic effects on the PQ interval and QRS width than disopyramide, while in the isolated preparations cross-circulated by the donor dog, pirmenol and disopyramide showed equipotent cardiodepressant effects.In the same prep aration, pirmenol decreased coronary blood flow following a transient increase, while disopyramide only decreased coronary blood flow. Since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which generates and propagates action potentials and also induces ven tricular automaticity, our results suggest that pirmenol possesses an electrophysio logic effect typical to an efficacious class I agent such as disopyramide. Pirmenol(CI-845, ()-cis-f_3-(2,6-di methyl-1 -piperidinyl) propyl-alpha-phenyl-2 pyridinemethanol monohydrochloride mono hydrate]) is a new synthetic antiarrhythmic agent and bears some chemical resemblance to disopyramide (Fig.

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Section: Effects Of Disopyramidementioning

confidence: 52%

Comparison of Cardiovascular Effects of Pirmenol with Those of Disopyramide in Isolated Canine Heart Preparations Cross-Circulated with a Donor Dog

Sugiyama

Motomura²,

Tamura

et al. 1990

Japanese Journal of Pharmacology

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“…Mexiletine (1-300 pg), disopyramide (30-1,000 kg), lidocaine (10-1,000 pg), and phenytoin (10-1,000 pg) also had dose-dependent negative chronotropic and inotropic effects in the dog isolated right atrial preparation ( Fig. 5 ) (2,3,14). Sinus arrest was induced at the highest dose of mexiletine (300 pg) in one of four preparations, and by lidocaine (1,000 pg) and phenytoin (1,000 pg) in all preparations.…”

Section: Cardiac Effects Of Ro 22-9194 On Isolated Blood-perfused Domentioning

confidence: 98%

“…Most antiarrhythmic agents, especially Class I drugs, are far from ideal for treating ventricular fibrillation (VF) or preventing sudden cardiac death. These drugs also depress the activity of the cardiovascular system and may exhibit proarrhythmic actions.Class I drugs exhibit onset and offset kinetics, block sodium channels in a state-dependent manner (9,11), are potent in various models of ventricular arrhythmias (8), and affect conduction velocity, sinoatrial nodal automaticity, and myocardial contractility (2,3,20). Ro22-9194, (2R)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate, is a newly synthesized Class I antiarrhythmic agent with a thromboxane A, (TXA,) synthase inhibitory activity.…”

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confidence: 99%

Ro 22‐9194: A New Class I Antiarrhythmic Agent

Murakami¹,

Furukawa²,

Nakashima³

et al. 1996

Cardiovascular Drug Reviews

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Key Words: Arrhythmia models--Cardiac responses-Fast sodium channels-Ro 22-919" Thromboxane A, synthase.Many antiarrhythmic agents are currently available, but more potent and safer drugs are needed. Most antiarrhythmic agents, especially Class I drugs, are far from ideal for treating ventricular fibrillation (VF) or preventing sudden cardiac death. These drugs also depress the activity of the cardiovascular system and may exhibit proarrhythmic actions.Class I drugs exhibit onset and offset kinetics, block sodium channels in a state-dependent manner (9,11), are potent in various models of ventricular arrhythmias (8), and affect conduction velocity, sinoatrial nodal automaticity, and myocardial contractility (2,3,20). Ro22-9194, (2R)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate, is a newly synthesized Class I antiarrhythmic agent with a thromboxane A, (TXA,) synthase inhibitory activity. Several experimental studies with Ro 22-9 194 have recently been published, and the cardiovascular, electrophysiological, and antiarrhythmic properties of this drug have been revealed (12-17). This article summarizes the preclinical and phase I clinical pharmacology of Ro 22-9194, a new Class I antiarrhythmic agent that inhibits TXA, synthesis. CHEMISTRYRo 22-9194 is structurally related to lidocaine and has a pyridine ring in the side chain (Fig. 1). It has a molecular weight of 461.52. It exists as a white crystalline powder that is soluble in water or methanol and insoluble in ether, and is stable at room temperature.

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“…It appears, therefore, that DP has different actions on vascular smooth muscle from the heart. In the heart, DP decreases the inotropic effect of Ca2+ (Chiba, Kobayashi & Furukawa, 1979), but in vascular smooth muscle it achieves its contractile effect in a way dependent upon Ca2+ fluxes. The treatment of cardiac arrhythmias with DP in hypertensive patients has, in view of these differential actions, to be performed with caution.…”

mentioning

confidence: 96%

Effect of disopyramide on isolated aortic ring of the rat

Moura

Lima

1983

British J Pharmacology

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Disopyramide produces a contraction of the isolated aortic ring of the rat which is graded, develops slowly, and has a time course similar to the tonic phase of the noradrenaline response. This effect is not modified by a-adrenoceptor blockade (yohimbine) but is completely abolished by a Ca2+ antagonist (verapamil) or by removal of Ca2+ from the bathing solution. These results indicate that, in the rat aorta, disopgIramide has a vasoconstrictor effect dependent on Ca + influx across the vascular smooth muscle membrane.

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Effects of disopyramide on SA nodal pacemaker activity and contractility in the isolated blood-perfused atrium of the dog

Cited by 9 publications

References 15 publications

Comparison of Cardiovascular Effects of Pirmenol with Those of Disopyramide in Isolated Canine Heart Preparations Cross-Circulated with a Donor Dog

Comparison of Cardiovascular Effects of Pirmenol with Those of Disopyramide in Isolated Canine Heart Preparations Cross-Circulated with a Donor Dog

Ro 22‐9194: A New Class I Antiarrhythmic Agent

Effect of disopyramide on isolated aortic ring of the rat

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