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Does treatment with beta-adrenergic blocking agents cause a decrease in beta2-adrenoceptor affinity?

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Summary

The effect of β-adrenoceptor antagonists (BAAs) differing in lipophilicity and partial agonist activity (PAA), and a full agonist, on the dissociation constant for [125I]-(−)- iodocyanopindolol binding to β2-adrenoceptors (KD) has been investigated.

Twelve healthy, normotensive male volunteers (mean age 22.3 y) were treated with different BAAs according to a cross-over design. The drugs used were propranolol (highly lipophilic BAA, no PAA), pindolol (moderately lipophilic BAA, strong PAA), dilevalol (highly lipophilic BAA, weak PAA) and salbutamol (full agonist). Before and after a single dose and an 8 day course of one of the drugs, blood pressure and the β2-adrenoceptor characteristics of mononuclear leukocytes (MNL) were determined. Between the treatment periods, there was a washout interval of 14 days.

All BAAs decreased the blood pressure, but only propranolol lowered heart rate. Treatment with salbutamol decreased the diastolic and increased the systolic blood pressure and heart rate. Three hours after the single dose of any of the BAAs, a more than 2-fold increase in KD was observed, and the increase became larger after 8 days of administration (up to 3.7-fold increase). In contrast, no effect on KD was observed after treatment with salbutamol. BAAs with PAA and salbutamol induced a 30% decrease in β2-adrenoceptor density.

It is concluded that treatment with BAAs, irrespective their lipophilicity or PAA, induces a decrease in the affinity of MNL β2-adrenoceptors for antagonists. This phenomenon may help to explain the contradictory relationship between the kinetics and dynamics of BAAs.

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Authors and Affiliations

  1. Department of General Internal Medicine, St Radboud University Hospital, The Netherlands

    W. M. Blankesteijn, S. J. Graafsma, M. P. C. Hectors, E. A. M. Olde Riekerink & Th. Thien

  2. Department of Pharmacology, University of Nijmegen, Nijmegen, The Netherlands

    J. F. Rodrigues de Miranda

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  1. W. M. Blankesteijn
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  2. S. J. Graafsma
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  3. M. P. C. Hectors
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  4. E. A. M. Olde Riekerink
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  5. J. F. Rodrigues de Miranda
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  6. Th. Thien
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Blankesteijn, W.M., Graafsma, S.J., Hectors, M.P.C. et al. Does treatment with beta-adrenergic blocking agents cause a decrease in beta2-adrenoceptor affinity?. Eur J Clin Pharmacol 42, 613–618 (1992). https://doi.org/10.1007/BF00265924

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  • DOI: https://doi.org/10.1007/BF00265924

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