Relevance of intrinsic sympathomimetic activity for beta blockers.
Intrinsic sympathomimetic activity (ISA) characterizes a group of beta blockers that are able to stimulate beta-adrenergic receptors (agonist effect) and to oppose the stimulating effects of catecholamines (antagonist effect) in a competitive way. Partial agonists are ligands that elicit a submaximal response when bound to beta receptors at maximal occupancy. In the isolated rat atrium, acebutolol produces a maximal stimulatory effect that is only 17 +/- 8% of the maximal effect induced by the full beta agonist isoproterenol. The presence of ISA results in less resting bradycardia and less of a reduction in cardiac output than is observed with beta blockers without ISA. In the long term, partial beta agonists may produce arterial vasodilation and increase arterial compliance, possibly leading to additional beneficial effects in the treatment of hypertension. beta blockers with ISA do not have adverse effects on plasma lipoproteins during long-term treatment; in addition, the presence of ISA could counteract the up-regulation of beta adrenoceptors often observed with beta blockers without ISA. Finally, the presence of ISA has been a conflicting issue for the use of such beta blockers in secondary prevention after myocardial infarction. However, the impressive results of the Acebutolol Prevention of Secondary Infarction trial in high-risk patients after myocardial infarction show that acebutolol, a beta blocker with moderate partial agonist activity, can be effective in decreasing the postinfarction mortality rate. By exhibiting a strikingly different hemodynamic profile from that of beta blockers without ISA, the partial beta agonists form an intriguing pharmacologic class of drugs for which prospective clinical trials should be extensively pursued.
Jaillon
P
P
Clinical Pharmacology Unit, St. Antoine University Hospital, Paris, France.
D000070:Acebutolol / Q000494:pharmacology / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000037:antagonists & inhibitors*; D004341:Drug Evaluation; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008074:Lipoproteins / Q000097:blood; D009203:Myocardial Infarction / Q000517:prevention & control; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D008074:Lipoproteins; D011943:Receptors, Adrenergic, beta; D000070:Acebutolol