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. 1993 Feb;108(2):507–515. doi: 10.1111/j.1476-5381.1993.tb12833.x

Investigations into factors determining the duration of action of the beta 2-adrenoceptor agonist, salmeterol.

A T Nials 1, M J Sumner 1, M Johnson 1, R A Coleman 1
PMCID: PMC1907975  PMID: 8095419

Abstract

1. This study has explored the mechanism underlying the long duration of action of the beta 2-adrenoceptor agonist, salmeterol. 2. Salmeterol, salbutamol and isoprenaline caused a concentration-related inhibition of electrically-induced contractile responses of the guinea-pig superfused trachea preparation. The effects of both isoprenaline and salbutamol were rapid in onset and rapidly reversed upon removal of the agonist. In contrast, the effects of salmeterol were slower in onset and could not be reversed by superfusion of the tissue with agonist-free Krebs solution even for periods of up to 10 h. 3. The effects of salmeterol were, however, readily reversed by a number of beta-adrenoceptor blocking drugs, as was the effect of a continuous infusion of isoprenaline. Upon removal of the antagonist, however, the effects of salmeterol and of the isoprenaline infusion were reasserted at a rate which was inversely related to the lipophilicity of a beta-adrenoceptor blocking drugs. 4. Salmeterol inhibited the binding of [125I]-(-)-iodopindolol (100 pM) to rat lung membranes (pIC50 7.1), with isoprenaline (pIC50 6.2) and salbutamol (pIC50 5.1) having lower potencies. The inhibition of binding by salmeterol was apparently non-competitive, whereas that produced by salbutamol and isoprenaline was competitive in nature. 5. Isoprenaline and salbutamol rapidly dissociated from their binding sites, whereas in marked contrast, the binding of salmeterol showed no dissociation for periods of up to 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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