Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1994 Aug;38(2):103–108. doi: 10.1111/j.1365-2125.1994.tb04332.x

The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

N M Wheeldon 1, D G McDevitt 1, B J Lipworth 1
PMCID: PMC1364854  PMID: 7981009

Abstract

1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
103

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold J. M., O'Connor P. C., Riddell J. G., Harron D. W., Shanks R. G., McDevitt D. G. Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man. Br J Clin Pharmacol. 1985 May;19(5):619–630. doi: 10.1111/j.1365-2125.1985.tb02689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bilski A. J., Halliday S. E., Fitzgerald J. D., Wale J. L. The pharmacology of a beta 2-selective adrenoceptor antagonist (ICI 118,551). J Cardiovasc Pharmacol. 1983 May-Jun;5(3):430–437. doi: 10.1097/00005344-198305000-00013. [DOI] [PubMed] [Google Scholar]
  3. Gille E., Lemoine H., Ehle B., Kaumann A. J. The affinity of (-)-propranolol for beta 1- and beta 2-adrenoceptors of human heart. Differential antagonism of the positive inotropic effects and adenylate cyclase stimulation by (-)-noradrenaline and (-)-adrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1985 Oct;331(1):60–70. doi: 10.1007/BF00498852. [DOI] [PubMed] [Google Scholar]
  4. Harry J. D., Norris S. C., Percival G. C., Young J. The dose in humans at which ICI 118,551 (a selective beta 2-adrenoceptor blocking agent) demonstrates blockade of beta 1-adrenoceptors. Clin Pharmacol Ther. 1988 May;43(5):492–498. doi: 10.1038/clpt.1988.64. [DOI] [PubMed] [Google Scholar]
  5. Lipworth B. J., Brown R. A., McDevitt D. G. Assessment of airways, tremor and chronotropic responses to inhaled salbutamol in the quantification of beta 2-adrenoceptor blockade. Br J Clin Pharmacol. 1989 Jul;28(1):95–102. doi: 10.1111/j.1365-2125.1989.tb03510.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lipworth B. J., Irvine N. A., McDevitt D. G. A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol. Eur J Clin Pharmacol. 1991;40(2):135–139. doi: 10.1007/BF00280067. [DOI] [PubMed] [Google Scholar]
  7. Lipworth B. J., McDevitt D. G. Beta-adrenoceptor responses to inhaled salbutamol in normal subjects. Eur J Clin Pharmacol. 1989;36(3):239–245. doi: 10.1007/BF00558154. [DOI] [PubMed] [Google Scholar]
  8. Lipworth B. J., McFarlane L. C., Coutie W. J., McDevitt D. G. Evaluation of the metabolic responses to inhaled salbutamol in the measurement of beta 2-adrenoceptor blockade. Eur J Clin Pharmacol. 1989;37(3):297–300. doi: 10.1007/BF00679788. [DOI] [PubMed] [Google Scholar]
  9. McDevitt D. G., Brown H. C., Carruthers S. G., Shanks R. G. Influence of intrinsic sympathomimetic activity and cardioselectivity on beta adrenoceptor blockade. Clin Pharmacol Ther. 1977 May;21(5):556–566. doi: 10.1002/cpt1977215556. [DOI] [PubMed] [Google Scholar]
  10. Pringle T. H., Riddell J. G., Shanks R. G. Characterization of the beta-adrenoreceptors which mediate the isoprenaline-induced changes in finger tremor and cardiovascular function in man. Eur J Clin Pharmacol. 1988;35(5):507–514. doi: 10.1007/BF00558246. [DOI] [PubMed] [Google Scholar]
  11. Wheeldon N. M., McDevitt D. G., Lipworth B. J. Evaluation of in vivo partial beta 1/beta 2-agonist activity: a dose-ranging study with carteolol. Br J Clin Pharmacol. 1992 Apr;33(4):411–416. doi: 10.1111/j.1365-2125.1992.tb04060.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Wheeldon N. M., McDevitt D. G., Lipworth B. J. Investigation of putative cardiac beta 3-adrenoceptors in man. Q J Med. 1993 Apr;86(4):255–261. [PubMed] [Google Scholar]
  13. Wheeldon N. M., McDevitt D. G., Lipworth B. J. Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects. Br J Clin Pharmacol. 1992 Oct;34(4):337–343. doi: 10.1111/j.1365-2125.1992.tb05640.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Williams M. E., Gervino E. V., Rosa R. M., Landsberg L., Young J. B., Silva P., Epstein F. H. Catecholamine modulation of rapid potassium shifts during exercise. N Engl J Med. 1985 Mar 28;312(13):823–827. doi: 10.1056/NEJM198503283121304. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES