Effect of pretreatment with the selective beta 1-adrenoceptor antagonist bisoprolol on the subsequent cardiovascular actions and beta-adrenoceptor subtype specific occupancy of celiprolol in healthy man.
The cardiovascular effects at rest and during exercise and beta 1- and beta 2-adrenoceptor occupancy following a single dose of 1200 mg celiprolol p.o. were investigated in 8 healthy subjects with or without pretreatment with a single dose of 20 mg bisoprolol p.o., using a placebo-controlled, 2-way cross-over design. The ergometric responses of heart rate (HR) and systolic blood pressure (SBP) after celiprolol were reduced to a similar extent as after bisoprolol, but the cardiovascular function at rest was affected in a different way: there was a rise in HR, clear enhancement of cardiac systolic performance, and a considerable drop in the estimated total peripheral vascular resistance, associated with median beta 1-RRA and beta 2-RRA occupancies of 88 and 34%, respectively. The cardiovascular effects of celiprolol were not affected by pretreatment with bisoprolol. Celiprolol thus binds extensively to beta 1-adrenoceptors, moderately to beta 2-adrenoceptors, acts as beta 1-adrenergic antagonist (exemplified by the ergometric effects) but has vasodilator, positive chronotropic and cardiac systolic performance enhancing properties, which do not involve either direct or indirect beta 1-adrenergic agonism, but which might reflect beta 2-adrenergic agonism.
Centre for Cardiovascular Pharmacology, Mainz-Wiesbaden, Germany.
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de Mey
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Beithaupt
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Palm
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Fuhr
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Belz
D000328:Adult; D017298:Bisoprolol / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D017272:Celiprolol / Q000378:metabolism / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005080:Exercise Test; D006801:Humans; D008297:Male; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D017272:Celiprolol; D017298:Bisoprolol