Reproducibility and consistency of the responses to supine bicycle ergometry; evaluation in conjunction with beta 1-adrenoceptor occupancies.
A protocol is presented for supine bicycle ergometry in healthy subjects, which aims for a target increase of heart rate (HR = 140 beats min-1) after 4 min cycling under constant load. The required load is selected from a pre-study ergometry with stepwise increasing load. Repeated testing with this protocol was shown to yield highly reproducible ergometric HR-responses. Because of their high reliability, the ergometric endpoints and increments permit a highly sensitive comparison of beta 1-adrenoceptor antagonism across dose and time within a given compound. The relationship between the changes of the ergometric rise of HR and the beta 1-adrenoceptor occupancy (estimated from radioreceptor assay data) permits to evaluate the ergometric efficiency of different beta-adrenoceptor antagonists across time and doses and to identify eventual differences that do not relate primarily to the extent of beta 1-adrenoceptor antagonism itself.
De Mey
C
C
Centre for Cardiovascular Pharmacology, Mainz-Wiesbaden, Germany.
Breithaupt-Grögler
K
K
Schloos
J
J
Palm
D
D
Belz
G G
GG
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002227:Carbazoles / Q000378:metabolism / Q000494:pharmacology; D000077261:Carvedilol; D017272:Celiprolol / Q000378:metabolism / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000378:metabolism / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015203:Reproducibility of Results
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000077261:Carvedilol; C011550:talinolol; D011433:Propranolol; D017272:Celiprolol; D008790:Metoprolol; D009638:Norepinephrine; D004837:Epinephrine