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. 1985 May;19(5):619–630. doi: 10.1111/j.1365-2125.1985.tb02689.x

Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man.

J M Arnold, P C O'Connor, J G Riddell, D W Harron, R G Shanks, D G McDevitt
PMCID: PMC1463834  PMID: 2860915

Abstract

ICI 118,551, 5 to 80 mg orally, did not significantly alter resting heart rate or blood pressure. In doses less than 40 mg the reduction in exercise tachycardia was under 10 beats/min. ICI 118,551, 10 to 40 mg, did not appear to reduce the maximum rise in systolic pressure with isoprenaline but did attenuate the changes in diastolic pressure, forearm blood flow and finger tremor. It also attenuated the isoprenaline-induced changes in serum glucose, insulin and potassium. On these observed changes, the effect of ICI 118,551 20 mg was similar to that of 40 mg and of propranolol 10 mg, but greater than that of atenolol 25 mg. An isoprenaline tachycardia was attenuated by all doses of ICI 118,551 studied. After atropine (0.04 mg/kg) ICI 118,551 20 mg still significantly reduced the effects of isoprenaline suggesting that functional beta 2-adrenoceptors may be present in the human heart. In doses less than 40 mg, ICI 118,551 appears to be a selective and competitive antagonist of beta 2-adrenoceptors in man.

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Selected References

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  1. Ablad B., Carlsson B., Carlsson E., Dahlöf C., Ek L., Hultberg E. Cardiac effects of beta-adrenergic receptor antagonists. Adv Cardiol. 1974;12(0):290–302. doi: 10.1159/000395473. [DOI] [PubMed] [Google Scholar]
  2. Arnold J. M., Allen J. A., Shanks R. G., McDevitt D. G. Changes in heart rate and forearm blood flow following intravenous boluses of isoprenaline in the presence of practolol and propranolol. Br J Clin Pharmacol. 1983 Jan;15(1):37–40. doi: 10.1111/j.1365-2125.1983.tb01460.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnold J. M., McDevitt D. G. Enhancement of physiological finger tremor by intravenous isoprenaline infusions in man: evaluation of its role in the assessment of beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1984 Aug;18(2):145–152. doi: 10.1111/j.1365-2125.1984.tb02446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. Briant R. H., Dollery C. T., Fenyvesi T., George C. F. Assessment of selective beta-adrenoceptor blockade in man. Br J Pharmacol. 1973 Sep;49(1):106–114. doi: 10.1111/j.1476-5381.1973.tb08272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Conway F. J., Fitzgerald J. D., McAinsh J., Rowlands D. J., Simpson W. T. Human pharmacokinetic and pharmacodynamic studies on the atenolo (ICI 66,082), a new cardioselective beta-adrenoceptor blocking drug. Br J Clin Pharmacol. 1976 Apr;3(2):267–272. doi: 10.1111/j.1365-2125.1976.tb00602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DUNCOMBE W. G. THE COLORIMETRIC MICRO-DETERMINATION OF NON-ESTERIFIED FATTY ACIDS IN PLASMA. Clin Chim Acta. 1964 Feb;9:122–125. doi: 10.1016/0009-8981(64)90004-x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. GREENFIELD A. D. Venous occlusion plethysmography. Methods Med Res. 1960;8:293–301. [PubMed] [Google Scholar]
  13. HALES C. N., RANDLE P. J. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963 Jul;88:137–146. doi: 10.1042/bj0880137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Holgate S. T., Stubbs W. A., Wood P. J., McCaughey E. S., Alberti K. G., Tattersfield A. E. Airway and metabolic resistance to intravenous salbutamol: a study in normal man. Clin Sci (Lond) 1980 Sep;59(3):155–161. doi: 10.1042/cs0590155. [DOI] [PubMed] [Google Scholar]
  16. Kendall M. J. Are selective beta-adrenoceptor blocking drugs an advantage? J R Coll Physicians Lond. 1981 Jan;15(1):33–40. [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Marsden C. D., Foley T. H., Owen D. A., McAllister R. G. Peripheral beta-adrenergic receptors concerned with tremor. Clin Sci. 1967 Aug;33(1):53–65. [PubMed] [Google Scholar]
  19. Marsden C. D., Meadows J. C. The effect of adrenaline on the contraction of human muscle--one mechanism whereby adrenaline increases the amplitude of physiological tremor. J Physiol. 1968 Feb;194(2):70–1P. [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. O'Donnell S. R., Wanstall J. C. Evidence that ICI 118, 551 is a potent, highly Beta 2-selective adrenoceptor antagonist and can be used to characterize Beta-adrenoceptor populations in tissues. Life Sci. 1980 Aug 25;27(8):671–677. doi: 10.1016/0024-3205(80)90008-9. [DOI] [PubMed] [Google Scholar]
  23. Smith H. J., Halliday S. E., Rouse W. The effects of a beta-2 selective adrenergic receptor antagonist (ICI 118,551) on twitch tension in cat soleus muscle. J Pharmacol Exp Ther. 1983 Jan;224(1):228–230. [PubMed] [Google Scholar]
  24. Tattersfield A. E., Cragg D. J. Effect of ICI 118551 on bronchial beta-adrenoceptor function and exercise heart rate in normal man. Br J Clin Pharmacol. 1983 Dec;16(6):587–590. doi: 10.1111/j.1365-2125.1983.tb02226.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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