Disease relevance of Xamoterol

• Treatment of idiopathic orthostatic hypotension with xamoterol [1].
• To determine if these hemodynamic changes were maintained after prolonged administration, the dose-response relation to cumulative doses of xamoterol was determined in a group of 14 patients with mild (n = 6)-to-serve (n = 8) ischemic left ventricular dysfunction [2].
• Long-term effects of xamoterol on left ventricular diastolic function and late remodeling: a study in patients with anterior myocardial infarction and single-vessel disease [3].
• Thus, xamoterol can be a useful addition for the treatment of left ventricular dysfunction because of long-term ischemic heart disease [4].
• Effect of xamoterol in Shy-Drager syndrome [5].

High impact information on Xamoterol

• Xamoterol, a cardioselective beta 1-adrenoceptor partial agonist, has been reported to be effective on postural hypotension [5].
• After xamoterol administration (200 mg b.i.d.), systolic blood pressure and heart rate were significantly increased in the averages during the day; however, increases were more pronounced at night [5].
• Agonist-induced desensitization of beta-adrenoceptor function in humans. Subtype-selective reduction in beta 1- or beta 2-adrenoceptor-mediated physiological effects by xamoterol or procaterol [6].
• In one of the multicenter studies in which 433 patients were randomized to xamoterol (n = 220), placebo (n = 109), and a positive control, digoxin 0.125 mg b.i.d. (n = 104), the percentages of improvement in exercise work were 33%, 5%, and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[7]
• In contrast, xamoterol neither affected lymphocyte beta 2-adrenoceptors nor beta 2-adrenoceptor-mediated in vivo effects but decreased beta 1-adrenoceptor-mediated in vivo effects [6].

Chemical compound and disease context of Xamoterol

• Two hundred and ten patients with clinical evidence of heart failure, developing after an acute myocardial infarction, were randomized to treatment with the beta 1-receptor antagonist metoprolol 50-100 mg b.i.d. (n = 106) or the beta 1-receptor partial agonist xamoterol 100-200 mg b.i.d. (n = 104) [8].
• 4. Pindolol, xamoterol and cicloprolol behaved as competitive beta-1 adrenoceptor antagonists against isoproterenol-induced tachycardia in a pithed rat model [9].
• Xamoterol is preferable to verapamil for treatment of patients with chronic atrial fibrillation who exhibit both bradycardia at rest and excessive tachycardia during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• Bronchospasm induced by atenolol 50 mg and xamoterol 200 mg was completely reversed by inhalation of the beta 2-adrenoceptor agonist terbutaline to a cumulative dose of 4.0 mg [11].
• Other agents such as digoxin, xamoterol and nitrates may be particularly useful in the treatment of patients with associated problems such as atrial fibrillation and angina [12].

Biological context of Xamoterol

• Changes in exercise tolerance and resting haemodynamics during long-term treatment of heart failure with xamoterol [13].
• Xamoterol produced significant improvements in resting cardiac index (2.51 +/- 0.15 to 2.80 +/- 0.14 l min-1 m-2; P less than 0.001), stroke volume (62 +/- 4 to 75 +/- 5 mljbeat-1; P less than 0.001) and stroke work index (42.4 +/- 3.6 to 47.7 +/- 3.9 gm beat-1 m-2; P less than 0.01) [14].
• The effects of xamoterol 0.2 mg kg-1 i.v. on haemodynamics at rest and on exercise were tested in eight patients, before and after 60 days regular treatment with 200 mg b.d. Left ventricular function improved equally with xamoterol on both occasions [15].
• Xamoterol (200 mg b.d. for 3 months) caused a fall in left ventricular end-diastolic pressure, an increase in dP/dTmax and a shorter systole in all groups of patients [16].
• Echocardiographic assessment of lack of beta 1-receptor down-regulation during prolonged therapy with xamoterol [15].

Anatomical context of Xamoterol

• The purpose of the study was to examine whether the prolonged administration of the beta 1-adrenoceptor partial agonist xamoterol could improve left ventricular diastolic function and affect the global remodeling process of the left ventricle after anterior myocardial infarction [3].
• The effect of xamoterol in failing human myocardium [17].
• The effects of xamoterol and pacing on myocardial blood flow and metabolism in patients with coronary artery disease [18].
• Xamoterol (0.0001-100 mumol l-1) produced only negative inotropic effects, as measured by changes in isometric force of contraction in diseased human papillary muscle strips [17].
• 5. ACVI myocyte responses were increased (E(max): GFP vs ACVI=3.16+/-0.77 vs 5.10+/-0.60, P<0.0001) to xamoterol (a partial beta(1)AR-selective agonist) under beta(2)AR blockade (+50 nm ICI 118, 551) [19].

Associations of Xamoterol with other chemical compounds

• The pharmacological effects of xamoterol, a beta adrenoceptor antagonist with partial agonistic activity, were examined in guinea pig cardiac preparations and compared with those of isoproterenol to assess possible mechanisms of its cardiac stimulant actions [20].
• Pharmacological analysis of the cardiac actions of xamoterol, a beta adrenoceptor antagonist with partial agonistic activity, in guinea pig heart: evidence for involvement of adenylate cyclase system in its cardiac stimulant actions [20].
• Similar monophasic profiles were obtained for inhibition of Xam- and Dob-induced lipolysis [21].
• Comparative analysis of beta-1 adrenoceptor agonist and antagonist potency and selectivity of cicloprolol, xamoterol and pindolol [9].
• The maximum increase in heart rate elicited by xamoterol and bucindolol was inhibited by treatment with propranolol, carvedilol, and betaxolol (beta1-adrenoceptor antagonist) but not by ICI 118551 (beta2-adrenoceptor antagonist) in neonatal rat [22].

Gene context of Xamoterol

• Stimulation of the beta1-adrenergic receptor with xamoterol, a specific partial agonist, did not promote proliferation or migration [23].
• Although its partial agonistic actions are more evident at beta 1-adrenoceptor sites, like prenalterol, xamoterol displays a degree of tissue rather than receptor-dependent selectivity [24].
• Effect of xamoterol on exercise capacity and left ventricular function in angina pectoris and in dilated cardiomyopathy [25].
• The actions of xamoterol were similar to those previously demonstrated, and were unaffected by beta 2-blockade, indicating selectivity for the beta 1-receptor [26].
• AS decreased both control and ACVI-stimulated xamoterol responses (E(max): AS=2.59+/-1.42, SAS=1.38+/-0.5) [19].

Analytical, diagnostic and therapeutic context of Xamoterol

• The acute hemodynamic effects of xamoterol were measured at rest and during two multistaged symptom-limited supine bicycle exercise tests (Ex-T), a control Ex-T followed by an Ex-T with either xamoterol or placebo [4].
• A large multicenter study program comprised of four studies demonstrated that patients with mild-to-moderate heart failure randomized to xamoterol (n = 617) 200 mg b.i.d. for 3 months significantly (p less than 0.0001) improved exercise capacity by 37% as compared with the placebo group (n = 300) with an increase of 18% [7].
• To study the acute hemodynamic effects of xamoterol, 24 patients, 39-70 years old, with mild-to-moderate postinfarction left ventricular dysfunction entered a double-blind, between-patient comparison of a single 5-minute intravenous infusion of xamoterol (0.2 mg/kg) and placebo [4].
• In a double-blind randomized placebo-controlled crossover study of xamoterol, a novel beta 1-partial agonist, 24 h ambulatory electrocardiograms were obtained in 26 patients prior to and at the end of 13-week treatment periods [27].
• The clinical relevance of these haemodynamic and neurohumoral changes were examined in conjunction with the German-Austrian Xamoterol Group's study, screening 443 patients with mild to moderate heart failure and giving xamoterol or placebo for 3 months as part of a randomized, double-blind study [28].

References