How beta2-selective is the adrenoceptor antagonist drug, IPS 339?
Schild plots for the compound (t-butylamino-3-ol-2-propyl)oximino-9-fluorene (IPS 399) have been obtained on isolated intrinsic tone trachea and atria (rate) og guinea-pigs. Alpha-Adrenoceptors and uptakes were inhibited. The Schild plots for IPS 339 on trachea (fenoterol as agonist) and on atria (noradrenaline as agonist) were not superimposed suggesting that IPS 339 was beta2-selective. The slopes of the Schild plots obtained on intrinsic tone tracheal preparations (isoprenaline or fenoterol as agonist), although greater than 1.0, were not significantly different from that on atria (noradrenaline as agonist). From the average separation of these Schild plots on trachea and atria IPS 339 was assessed to be only 3.3 times more active on beta2- than on beta1-adrenoceptors. The experiments in the literature which showed a high beta2-selectivity for IPS 339 (155 fold) were carried out on carbachol-contracted tracheal preparations (isoprenaline as agonist) and the Schild plot obtained had a very low slope which was quite different from that on atria. Therefore, the results illustrate how the quantitative estimate of the selectivity of a beta-adrenoceptor antagonist can be misleading when Schild plots with different slopes are compared.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C014898:IPS 339