The cardiovascular effects of xamoterol, a beta 1‐adrenoceptor partial agonist, in healthy volunteers at rest.

Abstract

School, Minamikawachi-machi, Tochigi Prefecture, Japan 1 The cardiovascular effects of three single intravenous doses of a Pl-adrenoceptor partial agonist, xamoterol (0.025, 0.05 and 0.1 mg kg-') and placebo were studied in six healthy volunteers at rest using a single-blind design. 2 In addition to heart rate and blood pressure measurements, cardiac contractility was measured by means of M-mode echocardiography and systolic time intervals. Ambulatory 24 h Holter-monitoring of the electrocardiogram was performed. Plasma concentrations of xamoterol were measured. 3 Compared to baseline, xamoterol (0.025 mg kg-) increased heart rate (61 + 3-68 ± 3 beats min-1, means and SEM) and systolic blood pressure (119 ± 3-138 + 5 mm Hg) but decreased pre-ejection period (100 + 4-76 + 5 msec). Stroke volume (88 ± 6-104 + 10 ml), cardiac output (4.8 ± 0.4-6.6 ± 0.6 1 min-'), velocity of circumferential fibre shortening (1.15 ± 0.06-1.50 ± 0.06 circ s-1) were increased by xamoterol. No significant changes were produced by placebo. 4 No dose-dependent effects were seen and maximum effects were produced by 0.025 mg kg-' xamoterol. Significant effects were observed for 2 h. The areas under the plasma concentration curves (AUCO.12) showed a linear dose response.

Beta‐adrenoceptor antagonists increase sinus arrhythmia, a vagotonic effect.

“…By contrast, oxprenolol has modest activity and xamoterol, a newer j1-selective adrenoceptor agent, possesses high ISA. In the dog the latter has been shown to possess 43% of the full agonist activity of isoprenaline on heart rate (Nuttall & Snow, 1982); in other animal species (Malta etal., 1985) and in man (Hashimoto et al, 1986) phase (1 session) five of the subjects (the sixth was not available to take part) knowingly took: metoprolol 100 mg in order to verify that the changes already observed with atenolol were not unique to that drug.…”

Comparison of the effects of xamoterol and isoprenaline on rat cardiac β‐adrenoceptors: studies of function and regulation

“…In some animal models and normal healthy volunteers, it produces approximately 43% of the maximum response of the full agonist isoprenaline (Nuttall & Snow, 1982;Hashimoto et al, 1986). The modest inotropic action of this drug is associated with a beneficial effect on stabilising sympathetic stimulation of the heart, providing inotropic support at low levels of sympathetic drive and protection from excessive and potentially metabolically harmful stimulation during exertion.…”

Myocardial beta‐adrenoceptor function and regulation in heart failure: implications for therapy.

“…no peripheral vasodilating effects in doses producing significant positive inotropism (Nuttall & Snow, 1982). In normal volunteers and heart failure patients it has a 'stabilising' action on sympathetic drive producing little or no effect on resting heart rate whilst inhibiting rapid exercise induced tachycardia (Hashimoto et al, 1986;Sato et al, 1987). Xamoterol has positive inotropic effects in normal volunteers (Hashimoto et al, 1986) and positive inotropic and lusitropic effects have been demonstrated in patients with ischaemic heart failure (Pouleur et al, 1982(Pouleur et al, , 1986.…”

“…In normal volunteers and heart failure patients it has a 'stabilising' action on sympathetic drive producing little or no effect on resting heart rate whilst inhibiting rapid exercise induced tachycardia (Hashimoto et al, 1986;Sato et al, 1987). Xamoterol has positive inotropic effects in normal volunteers (Hashimoto et al, 1986) and positive inotropic and lusitropic effects have been demonstrated in patients with ischaemic heart failure (Pouleur et al, 1982(Pouleur et al, , 1986. In a similar group of patients acute intravenous administration of xamoterol did not modify myocardial oxygen consumption or lactate extraction despite a positive inotropic effect .…”