Cardiovascular effects of ICI 118, 587, a new .BETA.-adrenoceptor partial agonist in man.

Sasayama, Shígetake; Yokawa, Shigeru; Akiyama, Makoto; Mikawa, Masato; Sakai, Osamu

doi:10.1253/jcj.50.636

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…A reduction in the breathlessness and anginal symptoms was observed (p < 0.05). This finding was in agreement with those in some other small studies (9,28,43,77) and two large placebo-controlled studies with 256 and 240 patients (24,100).…”

Section: Chronic Effectssupporting

confidence: 93%

“…In patients with nocturnal bradycardia caused by atrial fibrillation or sick sinus syndrome, Sasayama et al (77) found an increase in minimal heart rate during sleep.…”

Section: Electrophysiologymentioning

confidence: 99%

“…In 10 patients with chronic atrial fibrillation treated with digoxin, xamoterol reduced the maximal heart rate during exercise but increased the minimal heart rate and exercise tolerance (60). In patients with nocturnal bradycardia caused by atrial fibrillation or sick sinus syndrome, Sasayama et al (77) found an increase in minimal heart rate during sleep.…”

Section: Electrophysiologymentioning

confidence: 99%

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Xamoterol, a β₁Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Vigholt-Sørensen

1991

Cardiovascular Drug Reviews

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The high prevalence of chronic congestive heart failure has encouraged the search for new orally active drugs. In the early stages of heart failure, when symptoms are confined to periods of work stress, the overriding objective of drug therapy is to improve cardiac contractile activity. As heart failure advances and vasoconstriction and increased activity of the neuroendocrine system results in salt and water retention, diuretics can be added. In the terminal stages of disease, the addition of angiotensin converting enzyme (ACE) inhibitors can be expected to benefit the patient (87).In 1948, Ahlquist (1) proposed the existence of two types of receptors in the adrenergic system, a-and P-receptors. Lands et al. (46) presented experimental evidence in 1967 that justified a subdivision of f3-adrenergic receptors into PI-and P,-adrenoceptors. In 1972, Furchgott described (31) the procedure for the characterization of a-and P-adrenoceptors. According to the earlier classification, the responses of the tissues could be classified as being mediated by either P,-or P,-adrenoceptors. Subsequently, PI-and P,-adrenoceptors have been found to coexist in various organs. For example, in the heart of some animals and in the human, we have both receptor types. The functional and pathophysiological roles of these receptors are not fully defined (4,(15)(16)(17)37,38,103).The pharmacological classification of P-adrenoceptors into PI-and &-subtypes has been based on the relative affinity of the receptors for the agonists and on the competition between selective antagonists and nonselective radiolabeled ligands. The P-adrenoceptors have been identified biochemically, and these two mammalian proteins possess identical molecular masses. The structures of PI-and P,-adrenoceptors have been proposed and their genes have been cloned. Recent data establish that the two receptors are products of different genes (30).When an agonist occupies the P-adrenoceptor, adenyl cyclase is activated through its interaction with the guanine nucleotide-binding regulatory proteins, G,. Cyclic AMP is an

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Section: Chronic Effectssupporting

confidence: 93%

“…In patients with nocturnal bradycardia caused by atrial fibrillation or sick sinus syndrome, Sasayama et al (77) found an increase in minimal heart rate during sleep.…”

Section: Electrophysiologymentioning

confidence: 99%

Section: Electrophysiologymentioning

confidence: 99%

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Xamoterol, a β₁Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Vigholt-Sørensen

1991

Cardiovascular Drug Reviews

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“…Xamoterol has a partial beta-agonist effect and stabilizes the cardiac response to sympathetic drive. Preliminary studies suggested that this agent could benefit patients with chronic heart failure if adequate doses are used by improving diastolic function and exercise capacity [10,11]. However, the excess mortality was associated with 3-month treatment with this agent of patients with severe heart failure [12].…”

Section: Beta-receptor Agonistsmentioning

confidence: 99%

Intropic agents in the treatment of heart failure: Despair or hope?

Sasayama

1997

Cardiovasc Drug Ther

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Depression of myocardial contractility plays an important role in the development of heart failure; therefore, intensive interest and passion have been generated to develop cardiotonic agents to improve the contractile function of the failing heart. Inotropic agents that increase cyclic AMP, either by increasing its synthesis or reducing its degradation, exert dramatic short-term hemodynamic benefits, but these acute effects cannot be extrapolated into long-term improvement of the clinical outcome in patients with advanced heart failure. Administration of these agents to an energy-starved failing heart would be expected to increase myocardial energy use and could accelerate disease progression. The role of digitalis in the management of heart failure has been controversial, but ironically the drug has now been proved to favorably affect the neurohormonal disorders and its reevaluation is now being intensively investigated. More recently, attention has been focused on other inotropic agents that have a complex and diversified mechanism. Recent clinical studies have demonstrated that they are potentially useful in the long-term treatment of heart failure patients. These agents have some phosphodiesterase-inhibitory action but also possess additional effects, including acting as cytokine inhibitors, immunomodulators, or calcium sensitizers. However, their therapeutic ratio is narrow and further studies are warranted to establish their optimal doses and their eventual status in the treatment of heart failure.

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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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Cardiovascular effects of ICI 118, 587, a new .BETA.-adrenoceptor partial agonist in man.

Cited by 12 publications

References 17 publications

Xamoterol, a β₁Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Xamoterol, a β₁Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Intropic agents in the treatment of heart failure: Despair or hope?

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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Cardiovascular effects of ICI 118, 587, a new .BETA.-adrenoceptor partial agonist in man.

Cited by 12 publications

References 17 publications

Xamoterol, a β1Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Xamoterol, a β1Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Intropic agents in the treatment of heart failure: Despair or hope?

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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Xamoterol, a β₁Adrenoceptor Partial Agonist: Pharmacology and Clinical Use

Xamoterol, a β₁Adrenoceptor Partial Agonist: Pharmacology and Clinical Use