Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Aug 1982
A novel analysis of concentration-dependence of partial agonism Ring-demethylation of bupranolol results in a high affinity partial agonist (K 105) for myocardial and tracheal beta-adrenoceptors.
1. Ring-demethylation of the pure antagonist bupranolol results in a ligand (K 105) which induces conformational beta-adrenoceptor changes leading to partial agonistic effects in heart and trachea. However, these conformational receptor changes are not accompanied by changes in receptor affinity, because the affinity estimates for K 105 and bupranolol did not differ for a variety of myocardial tissues (including ventricular beta-adrenoceptors labelled with 3H-(-)-propranolol] and trachea, not even for tracheal receptor subtypes. 2. ⋯ For the case of a single class of non-interacting receptors the slope of the double log-regression should be unity. Our plot has incorporated information from complete concentration-effect curves, instead of a single concentration-ratio as in the Schild-plot. Analysis of data of K 105 with the new plot (intrinsic activity greater than 0) and the Schild-plot (intrinsic activity = 0) yielded slopes near unity, consistent with simple competition.