Hemodynamic Effects of Nicorandil, Isosorbide Dinitrate, and Dihydralazine in Healthy Volunteers

Belz, G. G.; Matthews, Jennifer H.; Beck, Aryel; Wagner, G.; Schneider, Berthold

doi:10.1097/00005344-198511000-00015

Cited by 30 publications

(7 citation statements)

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“…Coronary vascular resistance remained unaltered. The results are in general agreement with those obtained with ISDN in previous experimental (Wendt 1972) and clinical trials (Badger et al 1985;Belz et al 1985).…”

Section: Discussionsupporting

confidence: 91%

Cardiovascular Effects of Isosorbide Dinitrate Infused Intravenously Into Anaesthetized Dogs

Kuromaru¹,

Sakai²

1986

Clin Exp Pharma Physio

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The cardiohaemodynamic response and the development of tolerance to isosorbide dinitrate (ISDN) were examined in anaesthetized, open-chest dogs. ISDN, infused intravenously (i.v.) for 2 h at a rate of 10 or 30 micrograms/kg per min, decreased systemic blood pressure (systolic, mean and diastolic; SBP), left ventricular (LV) systolic and end-diastolic pressure, LVdP/dt max, pressure-rate product and coronary blood flow. No significant changes in heart rate (HR) and coronary vascular resistance were observed. Intravenous ISDN significantly attenuated the vasodilator effect of bolus intracoronary (i.a.) glyceryl trinitrate (GTN, 1 micrograms), and ISDN (30 micrograms), whereas that of bolus i.a. nicorandil (mononitrate, 20 micrograms) remained unaffected. Just after acute tolerance towards i.a. ISDN was provoked 1 h after starting ISDN infusion (30 micrograms/kg per min, i.v.), the combined infusion of ISDN (i.v.) and nicorandil (30 micrograms/kg per min) was instigated for a further hour. Also, 1 h after the onset of vehicle infusion (i.v.), the combined infusion of vehicle and nicorandil (30 micrograms/kg per min, i.v.) was started. There were essentially no significant differences between the corresponding values concerning the coronary vascular responses obtained from the two combined infusion groups.

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Section: Discussionsupporting

confidence: 91%

Cardiovascular Effects of Isosorbide Dinitrate Infused Intravenously Into Anaesthetized Dogs

Kuromaru¹,

Sakai²

1986

Clin Exp Pharma Physio

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“…Although nicorandil caused a distinct reduction in preload, as shown by decreased left ventricular end-diastolic diameter, a higher dose of nicorandil induced afterload reduction, as shown by the shortening of PEP. Similar results were reported by Belz et al [115] in a comparative study of nicorandil, isosorbide dinitrate, and dihydralazine.…”

Section: Studies In Angina Pectarissupporting

confidence: 90%

Pharmacology and therapeutic effects of nicorandil

Kinoshita

Sakai²

1990

Cardiovasc Drug Ther

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Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.

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“…The drug reduced systolic and diastolic blood pressure (although the latter effects were less pronounced). These effects resemble those of other nitrates [5,6]. Pirsidomine and ISDNwere equipotent in reducing SBP but the DBP-reducing effects of pirsidomine were less pronounced and of shorter duration than those of ISDN.…”

Section: Discussionmentioning

confidence: 60%

“…Human pharmacology studies have helped to assess the nature, time course and dose-dependency of the haemodynamic effects of organic nitrates. They reduce blood pressure, peripheral vascular resistance and change systolic time intervals as a consequence of their arterial/arteriolar effects [5,6]. Their venous vasodilatory effects are exemplified by their capacity to blunt the venous vasoconstriction of a dorsal hand vein in response to the in situ infusion of subsystemic doses of noradrenaline or phenylephrine [7,8].…”

mentioning

confidence: 99%

Differential effects of the novel NO-donating drug pirsidomine and isosorbide dinitrate on the venous vascular bed

Mey¹,

Breithaupt²,

Seibert-Grafe³

et al. 1994

Eur J Clin Pharmacol

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Sixteen healthy male subjects were investigated on four occasions when they received either placebo, 10 mg isosorbide dinitrate (ISDN), or 2.5 or 10 mg pirsidomine, a novel NO-donating drug.A constant-rate iv. infusion of a subsystemic dose (average 42 ng. min -~, SD 20.5) of noradrenaline in a dorsal hand vein was begun i h before drug treatment. It did not cause systemic changes but reduced the venous hand vein diameter by about 50%. This venoconstrictor response was approximately halved by 10 mg ISDN. Pirsidomine, in contrast, did not affect the in situ venoconstrictor responses to noradrenaline.ISDN and pirsidomine reduced systemic resting blood pressure. ISDN and 10rag pirsidomine were approximately equipotent in reducing systolic blood pressure, both in terms of the duration and the extent of the effect (maximum average reduction of ISDN-6.7, 95 % CI-10.3 to -3.0; and 10 mg pirsidomine -7.6, 95% CI -11.3 to -4.0 mmHg, respectively); 2.5 mg pirsidomine was less effective (-4.1, 95 % C1-7.8 to -0.5). ISDN and 10 mg pirsidomine were also similarly effective in reducing diastolic blood pressure (ISDN -8.4 mmHg, 95 % C1-10.5 to -6.2; 10 mg pirsidomine -6.0 mmHg, 95 % CI -8.2 to -3.9; 2.5 mg pirsidomine -2.8 mmHg, 95 % C1-5.0 to -0.6) but the effects of ISDN were longer lasting.Although similar with regard to their putative mechanism(s) of action and likely arterial/arteriolar effects, pirsidomine and ISDN seem to affect the venous vascular bed in distinctly different ways.For over a century, nitroglycerin and other organic nitrates have been widely used in the treatment of angina pectoris. They yield NO, which stimulates guanylate cyclase to form cGMP [1], thus causing an increase in smooth muscle CGMP which promotes vascular relaxation. Since the classic nitrates are hampered by their short duration of action and the development of tolerance on chronic usage, there has been a continuous search for new NO-donating compounds. Sidnonimines stimulate guanylate cyclase in a sulfhydryl (SH) group-independent fashion [2, 3] and so may not induce tolerance. Pirsidomine [CAS 936, 3-(cis-2.6-dimethylpiperidino)-N-(4-methoxybenzoyl)-sidnonimine] is a prodrug which, like sidnonimine, yields deacylated metabolites that liberate NO in an SH-independent fashion.The haemodynamic actions underlying the therapeutic efficacy of NO-donating drugs in angina pectoris are not yet completely clear and are considered to be mediated by one or more of the following effects: 1, venodilatation which increases the systemic venous capacity and reduces preload; 2, systemic arterial/arteriolar dilatation which reduces afterload; and 3, dilatation of epicardial coronary arteries, which directly enhances coronary blood flow [4]. Human pharmacology studies have helped to assess the nature, time course and dose-dependency of the haemodynamic effects of organic nitrates. They reduce blood pressure, peripheral vascular resistance and change systolic time intervals as a consequence of their arterial/arteriolar effects [5,6]. Their venous vasodilatory...

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Hemodynamic Effects of Nicorandil, Isosorbide Dinitrate, and Dihydralazine in Healthy Volunteers

Cited by 30 publications

References 0 publications

Cardiovascular Effects of Isosorbide Dinitrate Infused Intravenously Into Anaesthetized Dogs

Cardiovascular Effects of Isosorbide Dinitrate Infused Intravenously Into Anaesthetized Dogs

Pharmacology and therapeutic effects of nicorandil

Differential effects of the novel NO-donating drug pirsidomine and isosorbide dinitrate on the venous vascular bed

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