Hypotensive Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine, Sin-10

Kikuchi, Katsuko; Hirata, Minoru; Nagaoka, A

doi:10.1254/jjp.20.102

Cited by 31 publications

(11 citation statements)

References 10 publications

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“…SIN-10, N-acylated and chemically stable derivative of SIN-1, showed gradually developed and prolonged hypotension which was characterized by decrease in pulse pressure resulting from more depression during systole than during diastole. In constant flow perfusion experi ments, SIN-10 decreased slightly the perfusion pressure of the coronary artery, but decreased the total coronary inflow in association with the fall of systemic blood pressure in auto perfusion experiments (5). In the present study, RP was not affected in spite of the hypotension by intravenous 100 and 250 ag/kg of SIN-10, although RF did not consistently increase.…”

Section: Discussioncontrasting

confidence: 48%

Coronary Collateral Vasodilator Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine (Sin-10) in Heart With Chronic Coronary Insufficiency in Dogs

Hirata

Kikuchi

1970

Japanese Journal of Pharmacology

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Effects of the sydnonimine derivatives on cardiovascular system have been studied(1-5), and the results in our laboratory are summarized as follows : 1) the substitution by the group containing nitrogen with -N-N linkage in the 3-position (SIN-series) showed vasodilator and consequently hypotensive effects resembling to those of nitrites, and 2) N-acylation of imino group of sydnonimine made the compounds stable chemically (6), which probably resulted in gradual development and prolongation of the hypotensive effects as well as in decreased toxicity (4). These findings prompted us to study the effects of the derivatives on coronary collateral circulation, because nitroglycerin, the most im portant antianginal agent, was reported to dilate the collateral vessels which developed as a result of chronic myocardial ischem:ia (7,8), and because the effects of agents on the collateral circulation have received considerable attention as one of the approaches to evaluate antianginal activity in laboratory experiment (9)_ The present study was carried out to investigate the effects of N-ethoxycarbonyl-3 morpholinosydnonimine (SIN-10) and related compounds on the coronary collateral circulation. METHODSMale mongrel dogs weighing 8 to 13 kg were used. The effects of agents on the coronary collateral circulation were evaluated in the heart with chronic coronary insufficiency. The preparation of the coronary insufficiency was accomplished according to the technique of Harris (10) with a few modifications. The animals were treated with intramuscular 400,000 units of penicilline prior to the operation. Under anesthesia with intravenous 30 mg/kg of sodium pentobarbital and artificial respi ration, the chest was opened semiaseptically through the fourth intercostal space. The anterior descending branch of the left coronary artery was dissected free from the surround ing tissues as near the origin as possible, and constricted with a silk thread so that the blood flow is somewhat limited. For that purpose, the arterial branch was ligated together with a stainless wire of 1.0 to 1.5 mm in diameter, which was soon removed after the liga tion. The chest was tightly closed and air was removed from the chest cavity. The

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Section: Discussioncontrasting

confidence: 48%

Coronary Collateral Vasodilator Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine (Sin-10) in Heart With Chronic Coronary Insufficiency in Dogs

Hirata

Kikuchi

1970

Japanese Journal of Pharmacology

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“…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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“…Tierexperimentelle Ergebnisse weisen auf einen nitroähnlichen Wirkungsmechanismus hin (3,8,9,18). Eine Dosis von 2 mg oral oder sublingual ist beim Menschen etwa 6 Stunden lang antianginös wirksam, das Wirkungsmaximum ist eine halbe Stunde bis 4 Stunden nach Einnahme erreicht (7,12,16,19 o---e…”

Section: üBer Den Wirkungsmechanismus Bestehen Bei Einigenunclassified

Wirkung von Molsidomin auf das Belastungs-EKG bei Koronarinsuffizienz

Grewe¹,

Stauch²

1977

Dtsch med Wochenschr

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Molsidomine was shown to have a strong pain-relieving action in 22 coronary patients investigated one hour after oral intake of 2 mg of the substance. During comparable maximal exercise load the ST interval lowering was reduced from an average of 0.22 mV to 0.09 mV (P less than 0.0005). At the termination of exercise it was still reduced from 0.23 mV to 0.12 mV (P less than 0.0005). At the same time the exercise tolerance increased from 570 to 717 Watt-minutes (P less than 0.0025). Pectanginal complaints were clearly reduced at the same exercise loads, 11 patients became symptom-free at the same load. Even when exercise loading was stopped at higher loads a decrease of the severity of angina pectoris could be shown. Seven patients became symptom-free at that stage. The heart rate was not influenced markedly at rest and during exercise. Systolic blood pressure was reduced from 135 mm Hg to 118 mm Hg (P less than 0.0005), and in comparable submaximal loads from 177 to 165 mm Hg (P less than 0.005).

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Hypotensive Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine, Sin-10

Cited by 31 publications

References 10 publications

Coronary Collateral Vasodilator Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine (Sin-10) in Heart With Chronic Coronary Insufficiency in Dogs

Coronary Collateral Vasodilator Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine (Sin-10) in Heart With Chronic Coronary Insufficiency in Dogs

Molsidomine – an Effective Antianginal Drug

Wirkung von Molsidomin auf das Belastungs-EKG bei Koronarinsuffizienz

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Hypotensive Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine, Sin-10

Cited by 31 publications

References 10 publications

Coronary Collateral Vasodilator Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine (Sin-10) in Heart With Chronic Coronary Insufficiency in Dogs

Coronary Collateral Vasodilator Action of N-Ethoxycarbonyl-3-Morpholinosydnonimine (Sin-10) in Heart With Chronic Coronary Insufficiency in Dogs

Molsidomine &ndash; an Effective Antianginal Drug

Wirkung von Molsidomin auf das Belastungs-EKG bei Koronarinsuffizienz

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Molsidomine – an Effective Antianginal Drug