title: The actions of a new beta-adrenoceptor blocking drug, ICI 66082, on the rabbit papillary muscle and on the dog heart.
abstract: 1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not produce any depression of the twitch response of the rabbit papillary muscle. ICI 66082 antagonized the action of isoprenaline on this preparation at a concentration of 0.01 mug/ml.3 ICI 66082 (0.5-1.0 mg/kg intravenously) reduced the control value of dP/dt max in four dog preparations by a mean value of 529 mmHg/s (s.e. mean +/- 139 mm Hg/s), with no significant change in free heart rate. Antagonism of the effect of isoprenaline on dP/dt max and on free heart rate was demonstrated with ICI 66082 (0.1 mg/kg).4 ICI 66082 (1.0-1.5 mg/kg) produced no significant changes in dP/dt max or in free heart rate in four dogs pretreated with reserpine. A significant reduction (16% of the control value) in dP/dt max was observed with ICI 66082 at a high dose of 40-50 mg/kg.5 It is concluded that ICI 66082 is a competitive antagonist against the actions of isoprenaline on cardiac muscle, has no negative inotropic action (unless the dose exceeds 40 mg/kg) and lacks intrinsic sympathomimetic activity.
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D002395:Catecholamines / Q000378:metabolism; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005263:Femoral Artery / Q000187:drug effects; D005268:Femoral Vein / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D009206:Myocardium / Q000378:metabolism; D010096:Oxprenolol / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects*; D011217:Practolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology
chemical_list: D000081:Acetamides; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011412:Propanolamines; D010096:Oxprenolol; D012110:Reserpine; D007545:Isoproterenol; D011217:Practolol