STUDY OF THE RELATIONSHIP BETWEEN CARDIAC BETA-ADRENOCEPTOR BLOCKADE AND INTRINSIC SYMPATHOMIMETIC ACTIVITY IN RATS DEPLETED OF CATECHOLAMINES

1. The intrinsic sympathomimetic acitivity of a range of β‐adrenoceptor antagonists and its relationship to β‐adrenoceptor blockade was studied in pentobarbitone‐anaesthetized, vagotomized rats which had been depleted of catecholamines by pretreatment with syrosingopine. Dichlorisoprenaline, practolol, oxprenolol, pindolol and acebutolol, produced dose‐dependent positive chronotropic responses in this preparation. 2. The relationship between the dose requirements for this intrinsic sympathomimetic activity and β‐adrenoceptor‐blocking activity was not the same for all drugs: (i) dichlorisoprenaline and practolol had intrinsic activity at all β‐adrenoceptor‐blocking doses; and (ii) oxprenolol, pindolol and acebutolol had predominantly β‐adrenoceptor blockade at the lower dose levels and agonist activity only became significant at high doses relative to those producing β‐adrenoceptor blockade. 3. The positive chronotropic response to both practolol and pindolol was observed in rats which had been pithed and was antagonized by propranolol (0.1‐3.0 mg/kg, i.v.), indicating that β‐adrenoceptors were involved. 4. It was concluded that the intrinsic sympathomimetic activity of β‐adrenoceptor antagonists was not a simple property as it was described by the relationship between the dose requirements for intrinsic sympathomimetic activity and for β‐adrenoceptor blockade as well as the degree of partial agonist activity. Copyright © 1979, Wiley Blackwell. All rights reserved