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- W2006785761 abstract "The molecular pharmacology of a new putative long-acting bronchodilator TA 2005 (8-hydroxy-5-[(IR)-1-hydroxy-2-[N-[(IR)-2-(p-methoxy-phenyl)-1-methylethyl]amino]ethyl]carbostyril hydrochloride) has been compared with that of the reference compounds isoprenaline and salbutamol in both methacholine (3 × 10−6 M) precontracted guinea pig tracheal smooth muscle relaxation and in bovine trapezium muscle binding experiments. TA 2005 appeared very potent compared with isoprenaline and salbutamol (pD2 values of 9.29 vs. 7.65 and 7.10 respectively). For isoprenaline and salbutamol a shallow displacement curve was observed and addition of the non-hydrolysable GTP analogue guanylyl-imidodiphosphate (GppNHp) gave a rightward shift (pKd,high and pKd,low values of 7.3 and 6.1 vs. 7.0 and 5.4 respectively). For TA 2005 a steep displacement curve was found with only one binding state even without GppNHp (pKd,high value of 8.2). The long duration of action of TA 2005 might be explained by tight binding of this compound to the β2-adrenoceptor. The extent of tight binding for TA 2005 was extremely large. The molecular basis of the tight agonist binding phenomenon for TA 2005 seems to be of different origin than for isoprenaline. It is hypothesized that a different mechanism of activation of the β2-adrenoceptor may be involved for TA 2005." @default.
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- W2006785761 title "Atypical molecular pharmacology of a new long-acting β2-adrenoceptor agonist, TA 2005" @default.
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- W2006785761 doi "https://doi.org/10.1016/0922-4106(92)90158-r" @default.
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