Hemodynamic effects of molsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exertional angina pectoris

Detry, Jean-Marie R.; Brasseur, L.; Cosyns, Jacques; Rousseau, Michel F.

doi:10.1016/0002-9149(81)90298-8

Cited by 26 publications

(7 citation statements)

References 34 publications

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“…This interpretation fits with previous experiments in which a coronary collateral vasodilator action in hearts with coronary insufficiency (Hirata & Kikuchi, 1970), improved endocardial flow (Berdeaux et al, 1978), decreased infarct size after coronary artery ligation , and a significant anti-ischaemic effect after left anterior descending coronary artery controlled reduction of perfusion, as assessed by ST segment changes in multiple unipolar leads (Nitz & Martorana, 1985), have been documented with molsidomine. These results are also in accordance with clinical data showing that molsidomine reduces electrocardiographic signs of myocardial ischaemia in patients with coronary heart disease undergoing ergometric testing (Detry et al, 1981).…”

Section: Electrocardiographysupporting

confidence: 91%

“…Molsidomine (N-ethoxycarbonyl-3-morpholine-sydnonimine) is an effective long-acting antianginal drug (Guerchicoff et al, 1978;Majid et al, 1980;Detry et al, 1981;Baudry, 1982;Balakumaran et al, 1983;Balestrini et al, 1984), which possesses similar haemodynamic properties to those of nitrates (Guerchicoff et al, 1978;Majid et al, 1980;Detry et al, 1981). In addition, from one randomized trial it was concluded that molsidomine may be a useful adjunct to P-adrenoceptor blocking drugs in patients with coronary artery disease (Balestrini et al, 1984 synergistic action is comparable to that previously demonstrated for long-acting nitrates (Russek, 1968).…”

Section: Introductionmentioning

confidence: 99%

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Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

Cano

Guillen

Jouve

et al. 1986

British J Pharmacology

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Forty anaesthetized dogs were subjected to left circumflex coronary artery ligation followed by reperfusion. Molsidomine was randomly administered to 20 dogs (50 μg kg−1 as an i.v. bolus −15 min prior to coronary occlusion – followed by an infusion of 0.05 μg kg−1 min−1). Standard electrocardiographic leads 2 and 3 were continuously recorded to measure ST segment and ΔR% changes and to document both the number of ventricular premature beats and the onset of ventricular fibrillation; aortic pressure and cardiac output were measured; thromboxane B2 plasma levels, platelet aggregation produced by ADP, and molsidomine plasma levels were determined before and at 10, 30 and 75 min after the start of the drug protocol. Molsidomine protected the treated animals from early (10 min) post‐ischaemic ventricular fibrillation (0 of 20 vs 6 of 20, P = 0.0202), reduced the incidence of overall post‐occlusion ventricular fibrillation (3 of 20 vs 10 of 20, P = 0.0407) and improved the total survival rate (P = 0.0067). In molsidomine treated dogs: mean aortic pressure and the rate‐pressure product were lowered 10 min after the start of the drug; immediate post‐occlusion (3 min) ST segment changes (0.82 ± 0.52 vs 1.52 ± 0.78 mV, P < 0.025) and ΔR% changes (37 ± 50 vs 90 ± 84%, P < 0.025) were less marked; the number of ventricular premature beats was lowered and finally, a progressive decline of platelet aggregation produced by ADP was achieved after 75 min of drug infusion. These results were obtained in the presence of mean plasma levels of molsidomine ranging from 20 to 28 ng ml−1. The time‐action curve of the antifibrillatory effect of molsidomine parallels those at the level of post‐ischaemic electrocardiographic changes.

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Section: Electrocardiographysupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

Cano

Guillen

Jouve

et al. 1986

British J Pharmacology

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“…Marked ST seg ment depression (3 mm or more) also oc curred much less frequently while on molsi domine. The magnitude of increase in maxi mum workload in the present study was 21%, which is similar to that reported pre viously [8,9].…”

Section: Discussionsupporting

confidence: 91%

“…The hemodynamic response to molsidomine in patients with un complicated myocardial infarction is charac terized by a marked reduction in right atrial and pulmonary capillary wedge pressures [ 10], which suggests that there is probably a concomitant reduction in ventricular dia stolic volumes. Indeed, a number of experi mental [16,20,21] and clinical studies [5,7,9,22] have suggested a pronounced and sus tained venodilating activity of molsidomine, which is associated with decreased ventricu lar filling pressures as well as decreased dia stolic and systolic ventricular dimensions. Thus, it is probable that molsidomine causes more reduction of left ventricular wall ten sion and further decrease in myocardial oxy gen requirements than can be explained by the fall in arterial pressure alone.…”

Section: Discussionmentioning

confidence: 99%

Molsidomine – an Effective Antianginal Drug

Aptecar¹,

Vazquez²,

Aptecar³

1985

Cardiology

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The antianginal efficacy of molsidomine (single oral dose of 2 mg), a new antianginal drug, was evaluated in 12 patients with coronary artery disease in a double-blind randomized placebo-controlled study by bicycle ergometry. Besides the standard ergometric parameters, the myocardial efficiency index (MEI) was determined from the ratio of the maximum workload (kgm/min) to double product (mm Hg·min)· 10-², normalized for body surface area. Compared to placebo, molsidomine decreased positive exercise tests by 50%, pain response by 66%, and the magnitude of ST depression by 43%. Furthermore, the onset of ergometric positive response was delayed, with an increase in maximum workload achieved (+21 %), total work performed (+43%), and duration of exercise (+28%). MEI also increased from 0.98 ± 0.43 to 1.18 ± 0.44 (p < 0.005), due to a significant increase in maximal workload without a parallel increase in double product. These findings suggest that molsidomine is an effective antianginal drug and improves myocardial efficiency in patients with angina due to coronary artery disease.

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“…Molsidomine (N-ethoxycarbonyl-3-morpholino-sydnonimine) is a vasodilator agent that is used in clinical treatment of ischaemic coronary artery disease (Detry et al, 1981;Guerchicoff et al, 1978;Karsch et al, 1978;Majid et al, 1980). Its vasodilator effects resemble those of nitrovasodilators and are thought to be mediated by the release of nitric oxide (NO) and by the stimulation of cyclic GMP (Miller & Vanhoutte, 1990).…”

Section: Introduction Methodsmentioning

confidence: 99%

Pharmacokinetics of molsidomine and its active metabolite, linsidomine, in patients with liver cirrhosis.

Spreux‐Varoquaux

Doll

Dutot

et al. 1991

Brit J Clinical Pharma

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The pharmacokinetics of molsidomine were investigated in six healthy volunteers and in seven patients with alcoholic cirrhosis. After a 2 mg oral dose, molsidomine elimination half‐life was prolonged in cirrhotic patients (13.1 +/‐ 10.0 h vs 1.2 +/‐ 0.2 h, P less than 0.01) because of a decrease in its apparent plasma clearance (CL/F) (39.8 +/‐ 31.9 ml h‐1 kg‐1 in patients with cirrhosis vs 590 +/‐ 73 ml h‐1 kg‐1 in volunteers). The elimination half‐life of the active metabolite, linsidomine (SIN‐1) was also prolonged in cirrhotic patients (7.5 +/‐ 5.4 h vs 1.0 +/‐ 0.19 h, P less than 0.05). The AUC values of both molsidomine and linsidomine were increased in the cirrhotic group, but the increase in the former was considerably greater than in the latter as shown by the significant decrease of the ratio AUClinsidomine/AUCmolsidomine × 100 (4.5 +/‐ 6.1 in cirrhotic patients vs 23.5 +/‐ 3.4 in healthy volunteers, P less than 0.001). These results suggest that liver cirrhosis profoundly alters the pharmacokinetics and metabolism of molsidomine.

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Hemodynamic effects of molsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exertional angina pectoris

Cited by 26 publications

References 34 publications

Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

Molsidomine – an Effective Antianginal Drug

Pharmacokinetics of molsidomine and its active metabolite, linsidomine, in patients with liver cirrhosis.

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Hemodynamic effects of molsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exertional angina pectoris

Cited by 26 publications

References 34 publications

Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

Molsidomine &ndash; an Effective Antianginal Drug

Pharmacokinetics of molsidomine and its active metabolite, linsidomine, in patients with liver cirrhosis.

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Product

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Molsidomine – an Effective Antianginal Drug