The measurement of the relative efficacy of agonists by selective potentiation of tissue responses: studies with isoprenaline and prenalterol in cardiac tissue.
Isoprenaline, but not prenalterol, produced positive inotropy in guinea-pig papillary muscle. Prenalterol was a competitive antagonist of responses to isoprenaline in this tissue with a pKB of 7.24, as estimated by a Schild regression. Guinea-pig papillary muscles pretreated with the phosphodiesterase inhibitor, isobutylmethylxanthine (IMX), were 10 times more sensitive than controls to isoprenaline. In these tissues, prenalterol was a partial agonist producing 68% of the maximal response to isoprenaline. Schild regressions with atenolol indicated no change in beta-adrenoreceptors with IMX treatment and also that isoprenaline and prenalterol activated the same receptor in this tissue. The relative efficacy of isoprenaline and prenalterol was measured by using the KB estimated by Schild analysis for prenalterol and a Kd for isoprenaline from published binding studies. The relative efficacy of these drugs (epsilon ISO/epsilon PREN) was 242 +/- 29. The general method of potentiation of responses to weak agonists to estimate relative efficacy is discussed.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011217:Practolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011294:Prenalterol; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D012044:Regression Analysis
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D011294:Prenalterol; D011217:Practolol; D015056:1-Methyl-3-isobutylxanthine