Antianginal effects of corwin, a new beta-adrenoceptor partial agonist

Detry, Jean-Marie R.; Decoster, P.; Buy, Jean-Jacques; Rousseau, Michel F.; Brasseur, L.

doi:10.1016/0002-9149(84)90009-2

Cited by 35 publications

(15 citation statements)

References 16 publications

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“…No change was observed in resting pulmonary artery wedge pressure in this study; this may be a result of the relatively large doses of oral diuretics received by this group of patients. The acute effects of xamoterol on exercise haemodynamics are less well documented (Detry et al, 1983(Detry et al, , 1984Watanabe et al, 1986;Sato et al, 1987). However, in four other studies, exercise heart rate was uniformly lowered by 10 to 15%, as in this study.…”

Section: Exercise Haemodynamicscontrasting

confidence: 39%

“…mean) falling midway in this transition zone, and there was a small fall in resting heart rate. A number of other studies have reported the effects of intravenous xamoterol on resting and exercise haemodynamics (Detry et al, 1983(Detry et al, , 1984Rousseau et al, 1983;Ikaheimo & Takkunen, 1984;Simonsen, 1984;Molajo & Bennett, 1985;Amende et al, 1986;Bhatia et al, 1986;Watanabe et al, 1986;Kayanakis & Snow, 1987;Sato et al, 1987 and in other studies, left ventricular dP/dtmax improved by 17 to 46% (Rousseau et al, 1983;Ikaheimo & Takkunen, 1984;Simonsen, 1984;Amende et al, 1986). Pulmonary artery wedge pressure was reduced by up to one-third.…”

Section: Exercise Haemodynamicsmentioning

confidence: 90%

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The pharmacology of xamoterol: a basis for modulation of the autonomic control of the heart.

Snow¹

1989

Brit J Clinical Pharma

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(Corwin, Carwin, Corwil, Xamtol, ICI 118,587) 0.2 mg kg-. 2 Resting heart rate fell from 78 to 74 beats min-(P < 0.05) and cardiac index rose from 2.5 to 2.8 1 minm-m-2 (P < 0.001) after xamoterol. Blood pressure fell slightly, and systemic vascular resistance was reduced. Stroke work index improved and double product decreased. There were no changes in pulmonary artery wedge pressure, ejection fraction or plasma noradrenaline concentrations. 3 On exercise, xamoterol produced a considerable reduction in heart rate increase, improved stroke volume and left ventricular stroke index and lowered double product. Exercise duration increased by 10%, but this did not quite achieve statistical significance. 4 These results are consistent with the concept that a pl-partial adrenoceptor agonist with the level of intrinsic sympathomimetic activity (43%) of xamoterol provides moderate inotropic support at rest, and protects the heart against overstimulation on exercise, when sympathetic drive is high. 5 Reduction of double product on exercise implies a lowered oxygen demand, which could be of considerable importance in patients with ischaemic heart disease.

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Section: Exercise Haemodynamicscontrasting

confidence: 39%

Section: Exercise Haemodynamicsmentioning

confidence: 90%

The pharmacology of xamoterol: a basis for modulation of the autonomic control of the heart.

Snow¹

1989

Brit J Clinical Pharma

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“…Acute intravenous in jection induced a slight increase in cardiac output and a decrease in pulmonary capil lary wedge pressure (PCWP) at rest [9,10,[13][14][15][16][17], It possesses ^-antagonistic proper ties under high sympathetic tone [13,18,19]. Recently published placebo-controlled studies suggested a sustained improvement of exercise capacity on long-term adminis tration [20,21].…”

Section: Introductionmentioning

confidence: 99%

Lack of Tolerance Development after Long-Term Administration of the Partial Beta-Adrenoceptor Agonist Xamoterol

Erlemeier¹,

Küpper²,

Bleifeld³

1990

Cardiology

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Xamoterol is a selective partial β-adrenoceptor agonist. In a double-blind randomized placebo-controlled study, 30 patients (1 female, 29 male) with mild to moderate heart failure were treated with 200 mg of xamoterol twice daily or placebo during 3 months. At baseline and 72 h after the last tablet intake, the hemodynamic and humoral effects of a single intravenous dose of xamoterol (0.2 mg/kg) were assessed by right heart catheterization. At baseline, intravenous xamoterol raised resting heart rate by 3 % (NS) in the placebo and by 6% (NS) in the xamoterol group. On exercise, heart rate was reduced by 10% (p = 0.015) and 7% (p = 0.016), respectively. Pulmonary capillary wedge pressure (PCWP) dropped in both groups: at rest by 4 mm Hg (p = 0.0004) in the placebo group and by 6 mm Hg (p = 0.0002) in the xamoterol group; on exercise by 1 mm Hg (NS) in the placebo and by 6 mm Hg (p = 0.0001) in the xamoterol group. Similar changes of all variables were obtained after long-term therapy in both groups. Mean arterial blood pressure, cardiac index and systemic vascular resistance did not change importantly. Norepinephrine levels did not change, but plasma renin activity decreased at baseline as well as after long-term therapy in both groups by similar amounts. Thus, no signs of tolerance development were observed after an oral treatment with 200 mg of xamoterol twice daily during 3 months. However, xamoterol as a partial agonist exerted only weak changes of cardiac index and PCWP compared to full β-adrenoceptor agonists. The drug was well tolerated, and serious side effects were absent.

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“…It is likely, therefore, that the improvement was related to a beneficial effect on heart failure rather than on angina. Nonetheless, xamoterol does have anti-ischaemic effects (Detry et al, 1984;Barrios et al, 1986;Sasayama et al, 1986) and this study examines a subgroup of heart failure patients who had cardiomegaly without symptoms of angina pectoris during the baseline exercise test. From the total group of patients (Blackwood & Marlow, 1988;The German and Austrian Xamoterol Study Group, 1988), this study analyses the data on 269 (85 treated with placebo, 184 with xamoterol).…”

Section: Introductionmentioning

confidence: 99%

Xamoterol in mild to moderate heart failure: a subgroup analysis of patients with cardiomegaly but no concomitant angina pectoris. The European 'Corwin' Study Group.

Bastain¹,

Marlow²

1989

Brit J Clinical Pharma

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Xamoterol has been shown in large, double‐blind studies to produce benefit in patients with heart failure. Ischaemic heart disease is the commonest cause of heart failure in the Western World and many patients with heart failure also have angina pectoris (Califf et al., 1982). In view of the known anti‐ischaemic effects of xamoterol, we analysed the results of a subgroup of 269 patients with heart failure but without chest pain as a limiting factor on exercise to compare the efficacy of xamoterol in such patients with that of the total group. There were no differences in exercise heart rate, exercise tolerance and symptoms in patients without chest pain compared with the total group. Xamoterol is probably, therefore, acting through myocardial mechanisms other than an anti‐ischaemic effect.

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Antianginal effects of corwin, a new beta-adrenoceptor partial agonist

Cited by 35 publications

References 16 publications

The pharmacology of xamoterol: a basis for modulation of the autonomic control of the heart.

The pharmacology of xamoterol: a basis for modulation of the autonomic control of the heart.

Lack of Tolerance Development after Long-Term Administration of the Partial Beta-Adrenoceptor Agonist Xamoterol

Xamoterol in mild to moderate heart failure: a subgroup analysis of patients with cardiomegaly but no concomitant angina pectoris. The European 'Corwin' Study Group.

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