Comparison of the haemodynamic effects of bucindolol, propranolol and pindolol in healthy volunteers.
The effects of single oral doses of bucindolol (50, 100, 200 and 400 mg), pindolol (10 mg), propranolol (160 mg) and placebo on arterial pressure and heart rate in the supine and standing positions and exercise heart rate were compared in 12 healthy male volunteers. Supine heart rate was significantly greater after all four doses of bucindolol and pindolol in comparison to propranolol. Bucindolol had no significant effect on standing heart rate which was significantly reduced by pindolol and propranolol. Bucindolol, pindolol and propranolol significantly reduced an exercise tachycardia for at least 24 h after drug administration. Supine systolic pressure was not affected by any treatment but supine diastolic pressure was significantly reduced by bucindolol (200 and 400 mg) and by pindolol. All doses of bucindolol, propranolol and pindolol significantly reduced standing systolic blood pressure. There was a significant linear trend for reductions in standing systolic blood pressure and increasing doses of bucindolol. Standing diastolic blood pressure was significantly reduced by bucindolol 200 and 400 mg. Faintness and light headedness occurred in 6 of 12 subjects after 200 mg bucindolol and in 8 of 10 subjects after 400 bucindolol. After bucindolol, analysis of plasma samples demonstrated the presence of bucindolol, 5-hydroxy and 6-hydroxy bucindolol and indolyl-t-butylamine. These observations indicate that in man, bucindolol is a beta-adrenoceptor blocking drug with hypotensive activity and probably partial agonist activity. It is unlikely that the hypotensive effects result from blockade of beta-adrenoceptors or from the drug's partial agonist activity.
O'Connor
P C
PC
Finch
M J
MJ
Harron
D W
DW
Meredith
P A
PA
McDevitt
D G
DG
Shanks
R G
RG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D005082:Physical Exertion; D010869:Pindolol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D011412:Propanolamines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D011433:Propranolol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011433:Propranolol; D010869:Pindolol; C024307:bucindolol