Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1986 Mar;21(3):249–258. doi: 10.1111/j.1365-2125.1986.tb05187.x

Effects of ICI 141,292 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man.

T H Pringle, P C O'Connor, A J McNeill, M B Finch, J G Riddell, R G Shanks
PMCID: PMC1400869  PMID: 2870732

Abstract

The beta-adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. Seven subjects received in random order oral doses of ICI 141,292 20, 50, 100, 200 and 400 mg, atenolol 50 and 100 mg and placebo. ICI 14 292 had no effect on supine heart rate which was reduced by atenolol 100 mg. ICI 141,292 50, 100 and 200 mg had no effect on standing heart rate which was reduced by 400 mg at 2 h. Both doses of atenolol caused greater reductions. The maximum percent reduction of an exercise tachycardia after ICI 141,292 200 mg (23.9 +/- 3.7%) and 400 mg (24.3 +/- 5.2%) were similar to atenolol 50 mg (27.3 +/- 4.7%) but less than atenolol 100 mg (30.8 +/- 2.9%) (P less than 0.02). Six subjects received in random order single oral doses of ICI 141,292 100, 200 and 400 mg, atenolol 50 mg, propranolol 40 mg and placebo. Following each dose each subject received graded infusions of isoprenaline sulphate until heart rate increased by 40 beats min-1. Dose-response curves were constructed for the changes in heart rate, finger tremor, blood pressure and forearm blood flow produced by each infusion. At the 4 micrograms min-1 dose of isoprenaline, ICI 141,292 200 mg caused more attenuation than atenolol 50 mg but less than propranolol 40 mg in the changes of heart rate, diastolic blood pressure and finger tremor (P less than 0.02). ICI 141,292 400 mg caused more attenuation of the changes of all parameters than atenolol 50 mg but less attenuation of the changes in diastolic blood pressure and finger tremor than propranolol 40 mg (P less than 0.02). These results indicate that ICI 141,292 is a cardioselective beta-adrenoceptor antagonist with partial agonist activity.

Full text

PDF
249

Selected References

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

  1. Arnold J. M., McDevitt D. G. An assessment of physiological finger tremor as an indicator of beta-adrenoceptor function. Br J Clin Pharmacol. 1983 Aug;16(2):167–174. doi: 10.1111/j.1365-2125.1983.tb04981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnold J. M., McDevitt D. G. Heart rate and blood pressure responses to intravenous boluses of isoprenaline in the presence of propranolol, practolol and atropine. Br J Clin Pharmacol. 1983 Aug;16(2):175–184. doi: 10.1111/j.1365-2125.1983.tb04982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnold J. M., McDevitt D. G. Indirect blood pressure measurement during intravenous isoprenaline infusions. Br J Clin Pharmacol. 1985 Jan;19(1):114–116. doi: 10.1111/j.1365-2125.1985.tb02625.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arnold J. M., McDevitt D. G. Vagal activity is increased during intravenous isoprenaline infusion in man. Br J Clin Pharmacol. 1984 Sep;18(3):311–316. doi: 10.1111/j.1365-2125.1984.tb02469.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brick I., Hutchison K. J., McDevitt D. G., Roddie I. C., Shanks R. G. Comparison of the effects of I.C.I. 50172 and propranolol on the cardiovascular responses to adrenaline, isoprenaline and exercise. Br J Pharmacol. 1968 Sep;34(1):127–140. doi: 10.1111/j.1476-5381.1968.tb07956.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carruthers S. G., Twum-Barima Y. Measurement of partial agonist activity of pindolol. Clin Pharmacol Ther. 1981 Nov;30(5):581–586. doi: 10.1038/clpt.1981.207. [DOI] [PubMed] [Google Scholar]
  7. De Plaen J. F., Amery A., Reybrouck T. Comparative potency of atenolol and propranolol as beta-adrenergic blocking agents in man. Eur J Clin Pharmacol. 1976 Sep 30;10(5):297–303. doi: 10.1007/BF00565617. [DOI] [PubMed] [Google Scholar]
  8. Dunlop D., Shanks R. G. Selective blockade of adrenoceptive beta receptors in the heart. Br J Pharmacol Chemother. 1968 Jan;32(1):201–218. doi: 10.1111/j.1476-5381.1968.tb00444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ellis M. E., Sahay J. N., Chatterjee S. S., Cruickshank J. M., Ellis S. H. Cardioselectivity of atenolol in asthmatic patients. Eur J Clin Pharmacol. 1981;21(3):173–176. doi: 10.1007/BF00627916. [DOI] [PubMed] [Google Scholar]
  10. GREENFIELD A. D. Venous occlusion plethysmography. Methods Med Res. 1960;8:293–301. [PubMed] [Google Scholar]
  11. George C. F., Conolly M. E., Fenyvesi T., Briant R., Dollery C. T. Intravenously administered isoproterenol sulfate dose-response curves in man. Arch Intern Med. 1972 Sep;130(3):361–364. [PubMed] [Google Scholar]
  12. Harms H. H., Gooren L., Spoelstra A. J., Hesse C., Verschoor L. Blockade of isoprenaline-induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol. Br J Clin Pharmacol. 1978 Jan;5(1):19–26. doi: 10.1111/j.1365-2125.1978.tb01593.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Leitch A. G., Clancy L. J., Costello J. F., Flenley D. C. Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal men. Br Med J. 1976 Feb 14;1(6006):365–367. doi: 10.1136/bmj.1.6006.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lertora J. J., Mark A. L., Johannsen J., Wilson W. R., Abboud F. M. Selective beta-1 receptor blockade with oral practolol in man. A dose-related phenomenon. J Clin Invest. 1975 Sep;56(3):719–724. doi: 10.1172/JCI108143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. McDevitt D. G. The assessment of beta-adrenoceptor blocking drugs in man. Br J Clin Pharmacol. 1977 Aug;4(4):413–425. doi: 10.1111/j.1365-2125.1977.tb00756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mougeot G., Hugues F. C., Julien D., Marche J. Influence of propranolol and acebutolol on isoprenaline-induced changes in heart rate and peripheral blood flow in man. Arch Int Pharmacodyn Ther. 1981 May;251(1):116–125. [PubMed] [Google Scholar]
  18. O'Connor P. C., Arnold J. M., Brown A. N., Francis R. J., Finch M. B., Galloway D. B., Harron D. W., McDevitt D. G., Shanks R. G. Human pharmacokinetic and pharmacodynamic studies on Ro31-1118, a new beta-adrenoceptor antagonist. Br J Clin Pharmacol. 1985 Mar;19(3):319–327. doi: 10.1111/j.1365-2125.1985.tb02650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Smith H. J., Halliday S. E., Earl D. C., Stribling D. Effects of selective (beta-1 and beta-2) and nonselective beta adrenoceptor antagonists on the cardiovascular and metabolic responses to isoproterenol: comparison with ICI 141,292. J Pharmacol Exp Ther. 1983 Jul;226(1):211–216. [PubMed] [Google Scholar]
  20. Vilsvik J. S., Schaanning J. Effect of atenolol on ventilatory and cardiac function in asthma. Br Med J. 1976 Aug 21;2(6033):453–455. doi: 10.1136/bmj.2.6033.453. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES