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• W2022611966 endingPage "515" @default.
• W2022611966 startingPage "507" @default.
• W2022611966 abstract "1 This study has explored the mechanism underlying the long duration of action of the β2-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 β-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 β-adrenoceptor blocking drugs. 4 Salmeterol inhibited the binding of [125I]-(−)-iodopindolol (100 pm) to rat lung membranes (pIC50 7.1), with isoprenaline (pIC506.2) 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. 6 These data are consistent with a mechanism in which salmeterol binds adjacent to the active site of the β2-adrenoceptor, such that the drug cannot be washed out of the tissue, yet can interact with and activate the receptor. This latter property is susceptible to antagonism by β-adrenoceptor blocking drugs but is reasserted when the antagonists are removed." @default.
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• W2022611966 date "1993-02-01" @default.
• W2022611966 modified "2023-10-01" @default.
• W2022611966 title "Investigations into factors determining the duration of action of the β2-adrenoceptor agonist, salmeterol" @default.
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• W2022611966 doi "https://doi.org/10.1111/j.1476-5381.1993.tb12833.x" @default.
• W2022611966 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1907975" @default.
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