Pharmacology of nadolol (SQ 11725), a beta-adrenergic antagonist lacking direct myocardial depression

SQ 11725 was approximately 1/3 as potent as propranolol in blocking the stimulant effects of isoproterenol in vitro, but was 2-4 times more potent than propranolol in blocking the diastolic blood-pressure and heart-rate responses, respectively, to isoproterenol in vivo. SQ 11725 had no depressant effects on contractile force of isolated guinea pig atrial muscle at the largest bath concentration studied (1000 mug/ml), whereas propranolol caused significant depression at a concentration of 1-10 mug/ml. Propranolol was at least 20-30 times more depressant than SQ 11725 to canine myocardium in vivo. SQ 11725 was more effective then propranolol in inhibiting tachycardic responses to treadmill exercise in unanesthetized dogs. The duration of blockade of the heart-rate response to exercise or to isoproterenol administration in the unanesthetized dog was approximately 5 times greater with SQ 11725 than with propranolol.