The cardiovascular effects of xamoterol, a beta 1-adrenoceptor partial agonist, in healthy volunteers at rest.
The cardiovascular effects of three single intravenous doses of a beta 1-adrenoceptor partial agonist, xamoterol (0.025, 0.05 and 0.1 mg kg-1) and placebo were studied in six healthy volunteers at rest using a single-blind design. 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. Compared to baseline, xamoterol (0.025 mg kg-1) 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 +/- 0.61 min-1), 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. No dose-dependent effects were seen and maximum effects were produced by 0.025 mg kg-1 xamoterol. Significant effects were observed for 2 h. The areas under the plasma concentration curves (AUC0-12) showed a linear dose response. No adverse effects attributable to xamoterol were seen in haematological, biochemical, urinalysis or electrocardiographic tests. Four volunteers were aware of a more forceful heart beat after xamoterol, but this was mild and transient. It is concluded that xamoterol has a positive inotropic action.
Hashimoto
T
T
Shiina
A
A
Toyo-Oka
T
T
Hosoda
S
S
Kondo
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002037:Bundle-Branch Block / Q000503:physiopathology; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D002302:Cardiac Output / Q000187:drug effects; D004569:Electroencephalography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D017307:Xamoterol