J D Harry

THE ACTIONS OF A NEW β-ADRENOCEPTOR BLOCKING DRUG, ICI 66082, ON THE RABBIT PAPILLARY MUSCLE AND ON THE DOG HEART

1 The actions of 4‐(2‐hydroxy‐3‐isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new β‐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 μg/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 mmHg/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.

THE EFFECTS OF THREE β‐ADRENOCEPTOR BLOCKING DRUGS ON ISOLATED PREPARATIONS OF SKELETAL AND CARDIAC MUSCLE

1 The effects of propranolol, oxprenolol and practolol on the isometric twitch responses to electrical stimulation of isolated diaphragm muscles from the rat and of isolated papillary muscles from the rabbit are described. 2 Depression of the twitch responses of the diaphragm muscle was produced by propranolol (20 μg/ml), by oxprenolol (100 μg/ml) and by practolol (500 μg/ml). 3 Depression of the twitch responses of the papillary muscles was produced by propranolol (20 μg/ml) by oxprenolol (100 μg/ml) and by practolol (200 μg/ml). 4 No increase of twitch tension was produced by oxprenolol or practolol on either tissue. 5 It is concluded that propranolol, oxprenolol and practolol produce negative inotropic actions on isolated cardiac muscle by a mechanism unrelated to blockade of β‐adrenoceptors and which occurs at doses which are well in excess of those doses required to produce β‐blockade.