A study of the relationship between cardiac beta-adrenoceptor blockade and intrinsic sympathomimetic activity in rats depleted of catecholamines.
1. The intrinsic sympathomimetic activity of a range of beta-adrenoceptor antagonists and its relationship to beta-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 beta-adrenoceptor-blocking activity was not the same for all drugs: (i) dichlorisoprenaline and practolol had intrinsic activity at all beta-adrenoceptor-blocking doses; and (ii) oxprenolol, pindolol and acebutolol had predominantly beta-adrenoceptor blockade at the lower dose levels and agonist activity only became significant at high doses relative to those producing beta-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 beta-adrenoceptors were involved. 4. It was concluded that the intrinsic sympathomimetic activity of beta-adrenoceptor antagonists was not a simple property as it was described by the relationship between the dose requirements for intrinsic sympathomimetic activity and for beta-adrenoceptor blockade as well as the degree of partial agonist activity.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013566:Sympathomimetics / Q000037:antagonists & inhibitors
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D013566:Sympathomimetics; D011433:Propranolol