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. 1991 Nov;104(3):665–671. doi: 10.1111/j.1476-5381.1991.tb12486.x

Salmeterol, a novel, long-acting beta 2-adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo.

D I Ball 1, R T Brittain 1, R A Coleman 1, L H Denyer 1, D Jack 1, M Johnson 1, L H Lunts 1, A T Nials 1, K E Sheldrick 1, I F Skidmore 1
PMCID: PMC1908247  PMID: 1686740

Abstract

1. Salmeterol, a novel, long-acting beta-adrenoceptor agonist, has been compared with isoprenaline and salbutamol for activity in vitro on a range of beta-adrenoceptor containing preparations from laboratory animals and man, and in vivo for bronchodilator activity in the conscious guinea-pig. 2. Salmeterol, like isoprenaline and salbutamol, relaxed preparations of both guinea-pig trachea (contracted by prostaglandin (PG)F2alpha or electrical stimulation) and human bronchus (contracted by PGF 2 alpha) in a concentration-related fashion. Salmeterol was of similar potency to isoprenaline and more potent than salbutamol on both airway preparations. 3. Relaxant responses of superfused guinea-pig trachea and human bronchus to isoprenaline and salbutamol declined rapidly when the agonists were washed from the tissues, with complete recovery within 10 min, whereas responses to salmeterol were more persistent. In electrically-stimulated guinea-pig trachea preparations, inhibition by salmeterol persisted for periods of up to 12h, despite continuous superfusion with agonist-free medium. However, these persistent responses were rapidly and fully reversed by the beta-adrenoceptor blocking drug, propranolol (0.1 microM). In further studies on guinea-pig trachea, propranolol caused concentration-related parallel, rightward shifts of salmeterol concentration-effect curves, yielding a pA2 of 9.0. The slope of the Schild plot was 1.02. 4. Another beta-adrenoceptor blocking drug, sotalol (10 microM), also fully and rapidly reversed established submaximal responses to salmeterol in superfused guinea-pig trachea. However, after administration of sotalol was stopped, the antagonism waned, and salmeterol responses were reasserted without the addition of further agonist. 5. In the beta 1-adrenoceptor containing preparation, rat left atria, isoprenaline exhibited potent, concentration-related, positive inotropic activity, whereas salbutamol and salmeterol were at least 2000-5000 fold less potent, and appeared to be partial agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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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. BLINKS J. R., KOCH-WESER J. Analysis of the effects of changes in rate and rhythm upon myocardial contractility. J Pharmacol Exp Ther. 1961 Dec;134:373–389. [PubMed] [Google Scholar]
  3. Clark T. J. Choice of drug treatment in asthma. Pharmacol Ther. 1982;17(2):221–228. doi: 10.1016/0163-7258(82)90013-4. [DOI] [PubMed] [Google Scholar]
  4. Coburn R. F., Tomita T. Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle. Am J Physiol. 1973 May;224(5):1072–1080. doi: 10.1152/ajplegacy.1973.224.5.1072. [DOI] [PubMed] [Google Scholar]
  5. Coleman R. A., Nials A. T. Novel and versatile superfusion system. Its use in the evaluation of some spasmogenic and spasmolytic agents using guinea-pig isolated tracheal smooth muscle. J Pharmacol Methods. 1989 Mar;21(1):71–86. doi: 10.1016/0160-5402(89)90023-5. [DOI] [PubMed] [Google Scholar]
  6. Leifer K. N., Wittig H. J. Annals of allergy. Ann Allergy. 1975 Aug;35(2):69–80. [PubMed] [Google Scholar]
  7. McFadden E. R., Jr Aerosolized bronchodilators and steroids in the treatment of airway obstruction in adults. Am Rev Respir Dis. 1980 Nov;122(5 Pt 2):89–96. doi: 10.1164/arrd.1980.122.5P2.89. [DOI] [PubMed] [Google Scholar]
  8. Svedmyr N. Fenoterol: a beta2-adrenergic agonist for use in asthma. Pharmacology, pharmacokinetics, clinical efficacy and adverse effects. Pharmacotherapy. 1985 May-Jun;5(3):109–126. doi: 10.1002/j.1875-9114.1985.tb03409.x. [DOI] [PubMed] [Google Scholar]
  9. Tattersfield A. E. Bronchodilator drugs. Pharmacol Ther. 1982;17(3):299–313. doi: 10.1016/0163-7258(82)90019-5. [DOI] [PubMed] [Google Scholar]
  10. Ullman A., Svedmyr N. Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax. 1988 Sep;43(9):674–678. doi: 10.1136/thx.43.9.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wilson C., Wilson S., Piercy V., Sennitt M. V., Arch J. R. The rat lipolytic beta-adrenoceptor: studies using novel beta-adrenoceptor agonists. Eur J Pharmacol. 1984 May 4;100(3-4):309–319. doi: 10.1016/0014-2999(84)90007-4. [DOI] [PubMed] [Google Scholar]
  12. Zaagsma J., Nahorski S. R. Is the adipocyte beta-adrenoceptor a prototype for the recently cloned atypical 'beta 3-adrenoceptor'? Trends Pharmacol Sci. 1990 Jan;11(1):3–7. doi: 10.1016/0165-6147(90)90032-4. [DOI] [PubMed] [Google Scholar]

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