Cardiac effects of the beta 3-adrenoceptor agonist BRL35135 in man.
The aim of the present study was to evaluate the cardiac effects of the beta 3-adrenoceptor agonist BRL35135, and determine whether beta 3-receptors are involved in mediating chronotropic or inotropic responses in man. Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. Both BRL and SAL produced a significant increase in postural finger tremor in keeping with beta 2-adrenoceptor stimulation, and this response was totally abolished by pretreatment with N20. Significant increases in systolic blood pressure and Doppler stroke distance occurred with BRL and SAL which were unaffected by pretreatment with B5 and completely blocked by N20, in keeping with beta 2-mediated effects. BRL and SAL produced significant chronotropic and minute distance responses which were unaffected by beta 1-adrenoceptor blockade. However, whereas N20 blocked these responses to SAL, a small but significant response occurred with BRL in comparison with placebo despite complete blockade of co-existing beta 2-mediated effects. Compared with PL, the mean responses to N20/BRL, and the 95% confidence interval for the differences between the means were 7.4 beats min-1 [3.2 to 11.6] (P = 0.002) for heart rate, and 208.8 cm [38.3 to 379.3] (P = 0.02) for minute distance responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Wheeldon
N M
NM
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
McDevitt
D G
DG
Lipworth
B J
BJ
D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000009:adverse effects / Q000494:pharmacology*; D017298:Bisoprolol / Q000494:pharmacology; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009248:Nadolol / Q000494:pharmacology*; D010627:Phenethylamines / Q000009:adverse effects / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced
D000318:Adrenergic beta-Agonists; D010627:Phenethylamines; D009248:Nadolol; C063157:BRL 35135; D000420:Albuterol; D017298:Bisoprolol