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 beta1- and beta2-adrenoceptor occupancy following a single dose of 1200 mg celipr olol p. o. were investigated in 8 healthy subjects with or without pre treatment with a single dose of 20 mg bisoprolol p. o., using a placeb o-controlled, 2-way cross-over design. The ergometric responses of hea rt rate (HR) and systolic blood pressure (SBP) after celiprolol were r educed 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 consider able drop in the estimated total peripheral vascular resistance, assoc iated with median beta1-RRA and beta2-RRA occupancies of 88 and 34%, r espectively. The cardiovascular effects of celiprolol were not affecte d by pretreatment with bisoprolol. Celiprolol thus binds extensively t o beta1-adrenoceptors, moderately to beta2-adrenoceptors, acts as beta 1-adrenergic antagonist (exemplified by the ergometric effects) but ha s vasodilator, positive chronotropic and cardiac systolic performance enhancing properties, which do not involve either direct or indirect b eta1-adrenergic agonism, but which might reflect beta2-adrenergic agon ism.