1 The P-adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. 2 Seven subjects received in random order oral doses of ICI 141,29220,50,100,200 and 400 mg, atenolol 50 and 100 mg and placebo. ICI 14292 had no effect on supine heart rate which was reduced by atenolol 100 mg. ICI 141,292 50, 100 and 200 mg had no effect on standing heart rate which was reduced by 400 mg at 2 h. Both doses of atenolol caused greater reductions. 3 The maximum percent reduction of an exercise tachycardia after ICI 141,292 200 mg (23.9 ± 3.7%) and 400 mg (24.3 + 5.2%) were similar to atenolol 50 mg (27.3 + 4.7%) but less than atenodol 100 mg (30.8 + 2.9%) (P < 0.02). 4 Six subjects received in random order single oral doses of ICI 141,292 100, 200 and 400 mg, atenolol 50 mg, propranolol 40 mg and placebo. Following each dose each subject received graded infusions of isoprenaline sulphate until heart rate increased by 40 beats min-'. Dose-response curves were constructed for the changes in heart rate, finger tremor, blood pressure and forearm blood flow produced by each infusion. 5 At the 4 ,ug min-' dose of isoprenaline, ICI 141,292 200 mg caused more attenuation than atenolol 50 mg but less than propranolol 40 mg in the changes of heart rate, diastolic blood pressure and finger tremor (P < 0.02). ICI 141,292400 mg caused more attenuation of the changes of all parameters than atenolol 50 mg but less attenuation of the changes in diastolic blood pressure and finger tremor than propranolol 40 mg (P < 0.02). 6 These results indicate that ICI 141,292 is a cardioselective ,-adrenoceptor antagonist with partial agonist activity.

1 The 1-adrenoceptor antagonist activity, cardioselectivity and antilipolytic properties of Koe 3290 were investigated in healthy subjects. 2 Koe 3290 12.5,25,50 and 100 mg, atenolol 25,50 and 100 mg and placebo were given in double-blind randomised order to eight subjects. All doses of both Koe 3290 and atenolol reduced supine, standing and exercise heart rate (P < 0.02). From 2 to 8 h after administration the exercise heart rate after Koe 3290 100 mg was similar to that for atenolol 50 mg. 3 The cardioselectivity of Koe 3290 and atenolol was compared. Koe 3290 50, 100 and 150 mg, atenolol 50 and 100 mg and placebo were given to six subjects in a double-blind random order. Isoprenaline dose-response curves were constructed for cardiovascular parameters and finger tremor.4 For doses which were equipotent at the 1l-adrenoceptor (Koe 3290 100 mg and atenolol 50 mg) atenolol caused less attenuation of heart rate, diastolic blood pressure, forearm blood flow and finger tremor (P < 0.02). 5 There was no difference in the isoprenaline-induced changes in serum free fatty acids, blood glucose, plasma lactate or potassium after Koe 3290 and atenolol. Koe 3290 attenuated the rise in serum insulin more than atenolol (P < 0.02). 6 Koe 3290 is an effective ,B-adrenoceptor blocking drug in man. It is not as cardioselective as atenolol and does not possess specific antilipolytic properties.