The beta-
adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. Seven subjects received in random order oral doses of
ICI 141,292 20, 50, 100, 200 and 400 mg,
atenolol 50 and 100 mg and placebo. ICI 14 292 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. 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
atenolol 100 mg (30.8 +/- 2.9%) (P less than 0.02). 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-1. Dose-response curves were constructed for the changes in heart rate, finger
tremor, blood pressure and forearm blood flow produced by each infusion. At the 4 micrograms min-1 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 less than 0.02).
ICI 141,292 400 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 less than 0.02). These results indicate that
ICI 141,292 is a cardioselective
beta-adrenoceptor antagonist with partial agonist activity.