Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1968 Sep;34(1):127–140. doi: 10.1111/j.1476-5381.1968.tb07956.x

Comparison of the effects of I.C.I. 50172 and propranolol on the cardiovascular responses to adrenaline, isoprenaline and exercise

I Brick, K J Hutchison, D G McDevitt, I C Roddie, R G Shanks
PMCID: PMC1703393  PMID: 4877600

Abstract

1. The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses

2. After the pre-treatment of subjects with atropine or hexamethonium, I.C.I. 50172 produced a significant reduction in an isoprenaline tachycardia. This reduction was not competitive and did not exceed 50%.

3. The intravenous injection of 4 mg I.C.I. 50172 reduced an exercise tachycardia; its effect was less than that of 4 mg propranolol. This difference became greater as the doses of the two drugs were increased. The dextro isomer of propranolol had no effect on the exercise tachycardia; I.C.I. 45763 reduced it to the same extent as propranolol.

4. The intravenous injection of I.C.I. 50172 reduced the increase in heart rate produced by tilting a normal subject from the supine to 80° head-up position. After the administration of atropine, I.C.I. 50172 almost abolished the response. In the presence of atropine, I.C.I. 50172 was as active as propranolol in reducing the increase in heart rate on tilting.

5. The reason for the differences in the effects of I.C.I. 50172 on the increases in heart rate brought about by the three procedures is not clear.

6. The increase in forearm blood flow produced by the infusion of isoprenaline into the brachial artery was not reduced by the intra-arterial administration of I.C.I. 50172.

Full text

PDF
127

Selected References

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

  1. BLACK J. W., CROWTHER A. F., SHANKS R. G., SMITH L. H., DORNHORST A. C. A NEW ADRENERGIC BETARECEPTOR ANTAGONIST. Lancet. 1964 May 16;1(7342):1080–1081. doi: 10.1016/s0140-6736(64)91275-9. [DOI] [PubMed] [Google Scholar]
  2. Barrett A. M., Crowther A. F., Dunlop D., Shanks R. G., Smith L. H. Cardio-selective beta-blockade. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;259(2):152–153. doi: 10.1007/BF00537746. [DOI] [PubMed] [Google Scholar]
  3. Brick I., Glover W. E., Hutchison K. J., Roddie I. C. Effects of propranolol on peripheral vessels in man. Am J Cardiol. 1966 Sep;18(3):329–332. doi: 10.1016/0002-9149(66)90050-6. [DOI] [PubMed] [Google Scholar]
  4. Brick I., Hutchison K. J., Roddie I. C., Shanks R. C. Cardiac adrenergic blockade by 4-(2-hydroxy-3-isopropylamino-propoxy) acetanilide (I.C.I.50172). Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;259(2):156–157. doi: 10.1007/BF00537750. [DOI] [PubMed] [Google Scholar]
  5. Chamberlain D. A., Turner P., Sneddon J. M. Effects of atropine on heart-rate in healthy man. Lancet. 1967 Jul 1;2(7505):12–15. doi: 10.1016/s0140-6736(67)90057-8. [DOI] [PubMed] [Google Scholar]
  6. DONALD D. E., SHEPHERD J. T. RESPONSE TO EXERCISE IN DOGS WITH CARDIAC DENERVATION. Am J Physiol. 1963 Aug;205:393–400. doi: 10.1152/ajplegacy.1963.205.2.393. [DOI] [PubMed] [Google Scholar]
  7. DORNHORST A. C., ROBINSON B. F. Clinical pharmacology of a beta-adrenergic-blocking agent (Nethalide). Lancet. 1962 Aug 18;2(7251):314–316. doi: 10.1016/s0140-6736(62)90104-6. [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. Forsberg S. A., Johnsson G. Hemodynamic effects of propranolol and H 56-28 in man--comparative study of two beta-adrenergic receptor antagonists. Acta Pharmacol Toxicol (Copenh) 1967;25:75–83. doi: 10.1111/j.1600-0773.1967.tb02998.x. [DOI] [PubMed] [Google Scholar]
  10. GLICK G., BRAUNWALD E. RELATIVE ROLES OF THE SYMPATHETIC AND PARASYMPATHETIC NERVOUS SYSTEMS IN THE REFLEX CONTROL OF HEART RATE. Circ Res. 1965 Apr;16:363–375. doi: 10.1161/01.res.16.4.363. [DOI] [PubMed] [Google Scholar]
  11. Harris W. S., Schoenfeld C. D., Brooks R. H., Weissler A. M. Effect of beta adrenergic blockade on the hemodynamic responses to epinephrine in man. Am J Cardiol. 1966 Apr;17(4):484–492. doi: 10.1016/0002-9149(66)90238-4. [DOI] [PubMed] [Google Scholar]
  12. Howe R., Shanks R. G. Optical isomers of propranolol. Nature. 1966 Jun 25;210(5043):1336–1338. doi: 10.1038/2101336a0. [DOI] [PubMed] [Google Scholar]
  13. Hyman C., Winsor T. An electric volume transducer system for plethysmographic recording. J Appl Physiol. 1966 Jul;21(4):1403–1404. doi: 10.1152/jappl.1966.21.4.1403. [DOI] [PubMed] [Google Scholar]
  14. Jose A. D. Effect of combined sympathetic and parasympathetic blockade on heart rate and cardiac function in man. Am J Cardiol. 1966 Sep;18(3):476–478. doi: 10.1016/0002-9149(66)90073-7. [DOI] [PubMed] [Google Scholar]
  15. Levy J. V., Richards V. Inotropic and chronotropic effects of a series of beta-adrenergic blocking drugs: some structure-activity relationships. Proc Soc Exp Biol Med. 1966 Jun;122(2):373–379. doi: 10.3181/00379727-122-31138. [DOI] [PubMed] [Google Scholar]
  16. MORALES AGUILERA A., VAUGHANWILLIAMS E. M. THE EFFECTS ON CARDIAC MUSCLE OF BETA-RECEPTOR ANTAGONISTS IN RELATION TO THEIR ACTIVITY AS LOCAL ANAESTHETICS. Br J Pharmacol Chemother. 1965 Apr;24:332–338. doi: 10.1111/j.1476-5381.1965.tb01719.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McNeill R. S., Ingram C. G. Effect of propranolol on ventilatory function. Am J Cardiol. 1966 Sep;18(3):473–475. doi: 10.1016/0002-9149(66)90072-5. [DOI] [PubMed] [Google Scholar]
  18. Robinson B. F., Epstein S. E., Beiser G. D., Braunwald E. Control of heart rate by the autonomic nervous system. Studies in man on the interrelation between baroreceptor mechanisms and exercise. Circ Res. 1966 Aug;19(2):400–411. doi: 10.1161/01.res.19.2.400. [DOI] [PubMed] [Google Scholar]
  19. Shanks R. G., Wood T. M., Dornhorst A. C., Clark M. L. Some pharmacological properties of a new adrenergic beta-receptor antagonist. Nature. 1966 Oct 1;212(5057):88–90. doi: 10.1038/212088a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES