Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980 Apr;68(4):677–685. doi: 10.1111/j.1476-5381.1980.tb10860.x

In vitro activity of RO363, a beta1-adrenoceptor selective agonist.

D Iakovidis, E Malta, G A McPherson, C Raper
PMCID: PMC2044241  PMID: 6103722

Abstract

1 The beta-adrenoceptor stimulant effects of RO363 and (--)-isoprenaline have been compared in a variety of isolated tissue preparations. 2 RO363 is approximately half as potent as (--)-isoprenaline in tissues where actions are due to beta1-receptor activation (guinea-pig atrial and ileal preparations and ventricular strips from the rabbit, rat and guinea-pig. 3 In uterine and lung strip preparations from the guinea-pig, where responses are due to beta2-receptor stimulation. RO363 is 100 to 350 times less active than (--)-isoprenaline and has a low intrinsic activity. 4 In spontaneously contracted tracheal preparations from the guinea-pig, RO363 is a full agonist and is approximately half as potent as (--)-isoprenaline. These effects of RO363 are due to the activation of a population of beta1-receptors in the tissue since RO363 and (--)-isoprenaline have the same relative potencies in trachea, cardiac and ileal preparations. In addition the Kb values for practolol are similar in all these preparations when RO363 is used as the agonist. 5 The results show that RO363 is a potent and highly selective beta1-receptor agonist.

Full text

PDF
677

Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ablad B., Brogård M., Corrodi H. Cardiac stimulant 1-(hydroxyphenoxy)-3-isopropylamino-2-propanols. Acta Pharm Suec. 1970 Nov;7(5):551–558. [PubMed] [Google Scholar]
  3. 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]
  4. Carlsson E., Dahlöf C. G., Hedberg A., Persson H., Tångstrand B. Differentiation of cardiac chronotropic and inotropic effects of beta-adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol. 1977 Nov;300(2):101–105. doi: 10.1007/BF00505039. [DOI] [PubMed] [Google Scholar]
  5. Cornish E. J., Miller R. C. Comparison of the beta-adrenoceptors in the myocardium and coronary vasculature of the kitten heart. J Pharm Pharmacol. 1975 Jan;27(1):23–30. doi: 10.1111/j.2042-7158.1975.tb09373.x. [DOI] [PubMed] [Google Scholar]
  6. Davey T., Malta E., Raper C. A comparison of the activities of the beta-adrenoceptor agonists MJ9184-1 AND (--)-ISOPRENALINE IN GUINEA-PIG AND CAT PREPARATIONS. Clin Exp Pharmacol Physiol. 1974 Jan-Feb;1(1):43–52. doi: 10.1111/j.1440-1681.1974.tb00525.x. [DOI] [PubMed] [Google Scholar]
  7. Dowd H., Keh G. S., Raper C. Catechol-substituted phenoxypropanolamines: adrenoceptor activity in the anaesthetized cat. Br J Pharmacol. 1977 Jun;60(2):197–203. doi: 10.1111/j.1476-5381.1977.tb07741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drew G. M., Levy G. P. Characterization of the coronary vascular -adrenoceptor in the pig. Br J Pharmacol. 1972 Oct;46(2):348–350. doi: 10.1111/j.1476-5381.1972.tb06880.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harms H. H. Isoproterenol antagonism of cardioselective beta adrenergic receptor blocking agents: a comparative study of human and guinea-pig cardiac and bronchial beta adrenergic receptors. J Pharmacol Exp Ther. 1976 Nov;199(2):329–335. [PubMed] [Google Scholar]
  10. Hoefle M. L., Hastings S. G., Meyer R. F., Corey R. M., Holmes A., Stratton C. D. Cardioselective beta-adrenergic blocking agents. 1. 1-((3,4-Dimethoxyphenethyl)amino)-3-aryloxy-2-propanols. J Med Chem. 1975 Feb;18(2):148–152. doi: 10.1021/jm00236a007. [DOI] [PubMed] [Google Scholar]
  11. Keh G. S., Raper C., Dowd H. Agonistic and antagonistic actions of 3,4-dihydroxy-substituted phenoxypropanolamines in guinea-pig atria and trachea. Clin Exp Pharmacol Physiol. 1978 Jul-Aug;5(4):393–398. doi: 10.1111/j.1440-1681.1978.tb00689.x. [DOI] [PubMed] [Google Scholar]
  12. Leclerc G., Mann A., Wermuth C. G., Bieth N., Schwartz J. Synthesis and beta-adrenergic blocking activity of a novel class of aromatic oxime ethers. J Med Chem. 1977 Dec;20(12):1657–1662. doi: 10.1021/jm00222a023. [DOI] [PubMed] [Google Scholar]
  13. Lulich K. M., Mitchell H. W., Sparrow M. P. The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea. Br J Pharmacol. 1976 Sep;58(1):71–79. doi: 10.1111/j.1476-5381.1976.tb07694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Malta E., Raper C. Non-catechol phenylethanolamines: agonistic and antagonistic actions on beta-adrenoreceptors in isolated tissues from the guinea-pig. Clin Exp Pharmacol Physiol. 1974 May-Jun;1(3):259–268. doi: 10.1111/j.1440-1681.1974.tb00548.x. [DOI] [PubMed] [Google Scholar]
  15. Mylecharane E. J., Raper C. Influence of N-alkyl substitution on antagonism at 1 - and 2 -receptor sites. Eur J Pharmacol. 1973 Mar;21(3):375–378. doi: 10.1016/0014-2999(73)90142-8. [DOI] [PubMed] [Google Scholar]
  16. O'Donnell S. R., Persson C. G., Wanstall J. C. An in vitro comparison of beta-adrenoceptor stimulants on potassium-depolarized uterine preparations from guinea-pigs. Br J Pharmacol. 1978 Feb;62(2):227–233. doi: 10.1111/j.1476-5381.1978.tb08450.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Donnell S. R., Wanstall J. C. Hexoprenaline: beta-adrenoreceptor selectivity in isolated tissues from the guinea-pig. Clin Exp Pharmacol Physiol. 1975 Nov-Dec;2(6):541–547. doi: 10.1111/j.1440-1681.1975.tb01859.x. [DOI] [PubMed] [Google Scholar]
  18. Raper C., McPherson G. A., Iakovidis D. A phenoxypropanolamine derivative (RO363) with selective beta1-receptor stimulant actions. Eur J Pharmacol. 1978 Nov 15;52(2):241–242. doi: 10.1016/0014-2999(78)90214-5. [DOI] [PubMed] [Google Scholar]
  19. Shtacher G., Rubinstein R., Somani P. Alteration of relative affinities toward myocardial and vascular beta adrenoceptors induced by side-chain substitution of aryloxypropanolamines. J Med Chem. 1978 Jul;21(7):678–683. doi: 10.1021/jm00205a016. [DOI] [PubMed] [Google Scholar]
  20. Siegl P. K., Rossi G. V., Orzechowski R. F. Isolated lung strips of guinea pigs: responses to beta-adrenergic agonists and antagonists. Eur J Pharmacol. 1979 Feb 15;54(1-2):1–7. doi: 10.1016/0014-2999(79)90400-x. [DOI] [PubMed] [Google Scholar]
  21. van den Brink F. G. The model of functional interaction. II. Experimental verification of a new model: the antagonism of beta-adrenoceptor stimulants and other agonists. Eur J Pharmacol. 1973 Jun;22(3):279–286. doi: 10.1016/0014-2999(73)90027-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES