The β1‐ and β2‐adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat

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Abstract
1 The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the β1- and β2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the β1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. 2 All the compounds studied caused a concentration-dependent increase in atrial frequency and relaxation of the uterus. The atrial response to pindolol was competitively inhibited by the β1-selective blocker pafenolol (10−7 m.), while the β2-selective blocker ICI 118551 (10−8 m.) was without effect. Pafenolol (10−7 m.) was also shown to inhibit the atrial frequency effect of alprenolol and oxprenolol. In the uterus, ICI 118551 (3 × 10−9 m., 3 × 10−8 m., 3 × 10−7 m.) blocked the pindolol effect with a pKB of 9.28. In addition, ICI 118551 (10−8 m.) competitively inhibited the relaxation of the uterus induced by alprenolol and oxprenolol. 3 For alprenolol (right atrium and uterus), oxprenolol (right atrium), and pindolol (right atrium), the concentrations needed for half-maximal response were significantly greater than those required for occupation of half the receptors. This dissociation was most pronounced for pindolol in the right atrium. In this tissue, 80–85% of the β1-adrenoceptors had to be occupied by pindolol to initiate a tissue response corresponding to 50% of the maximal effect generated by the compound. 4 The intrinsic activities of alprenolol, oxprenolol and pindolol (expressed as % of the maximal tissue response to isoprenaline) were significantly higher in the uterus than in the right atrium. The intrinsic activity of the compounds varied between individual preparations and, particularly in the uterus, correlated with the sensitivity of the tissue to β-adrenoceptor stimulation by isoprenaline. 5 Calculation of efficacy, relative to isoprenaline, of the partial β-agonists revealed a β2-adrenoceptor selectivity for alprenolol (2.0), oxprenolol (1.4) and pindolol (3.0). 6 It is concluded that weak partial agonists such as alprenolol, oxprenolol and pindolol possess complex β1- and β2-adrenoceptor stimulatory properties in relation to β-adrenoceptor occupancy and tissue sensitivity to β-adrenoceptor stimulation.