Cardiovascular Drugs and Therapy

, Volume 7, Issue 6, pp 839–849 | Cite as

Extent of beta1- and beta2-receptor occupancy in plasma assesses the antagonist activity of metoprolol, pindolol, and propranolol in the elderly

  • Timo Kaila
  • Esko Iisalo
  • Aapo Lehtonen
  • Heikki Saarimaa
Beta-Blocker Therapy


We estimated antagonist activity of metoprolol, pindolol, and propranolol in elderly cardiovascular patients by determining the extent to which the drugs occupied rabbit lung beta1- and rat reticulocyte beta2-adrenoceptors in plasma samples during drug treatment. The randomized, double-blind, crossover study was carried out by administering twice daily 100 mg metoprolol, 5 mg pindolol, and 80 mg propranolol for 7 days to 20 hypertensive subjects with a mean age of about 70 years. A 2-week interval was kept between administration of the different regimens. Receptor occupancy was measured at 1 hour before and 2 hours after administration of the last dose of each regimen by adding rabbit lung beta1- and rat reticulocyte beta2-receptors to plasma samples and by labeling the receptors with a radiolabeled beta-antagonist, (−)-[3H]CGP-12177. The results and conclusions were the following: (a) The extent to which metoprolol, pindolol, and propranolol occupied rabbit lung beta1-and rat reticulocyte beta2-adrenoceptors in plasma samples estimated accurately the intensity of beta-receptor antagonism in the patients who did not tolerate physiological and pharmacological tests measuring the degree of beta1- and beta2-adrenoceptor blockade. (b) The mean beta1- and beta2-receptor occupancy of pindolol and propranolol varied between 76% and 99% during the treatments. The mean beta1-receptor occupancy of the metoprolol regimen varied between 54% and 92%, and its beta2-receptor occupancy varied between 6% and 38%. Thus the antagonist activity of the metoprolol regimen differed significantly from that of the other regimens (ANOVA for repeated measures, p<0.05 and 0.001, for the beta1- and beta2-occupancy, respectively). (c) The extent of beta1- and beta2-receptor occupancy in plasma samples was in conformity with the literature on the intensity, selectivity, and duration of beta-blockade after similar drug doses. (d) The data on the receptor occupancy of beta-blocking drugs in plasma samples appear to be valuable in analyzing their effects, and it may be a method for optimizing drug therapy for aged cardiovascular patients.

Key Words

Beta1 and beta2 receptors beta-blockers elderly 


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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Timo Kaila
    • 1
  • Esko Iisalo
    • 1
  • Aapo Lehtonen
    • 2
  • Heikki Saarimaa
    • 2
  1. 1.Department of Clinical PharmacologyUniversity of TurkuTurkuFinland
  2. 2.Department of MedicineTurku City HospitalTurkuFinland

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