beta-Adrenergic blockers: a 50-year historical perspective.

The development and subsequent clinical application of the beta-adrenergic receptor blocking drugs over the past 50 years represent one of the major advances in human pharmacotherapy. No other class of synthetic drugs has demonstrated such widespread therapeutic utility for the treatment of so many cardiovascular and noncardiovascular diseases. In addition, these drugs have proven to be molecular probes that have contributed to our understanding of disease, and on the molecular level, both the structure and the function of the 7 transmembrane G protein receptors, which mediate the actions of many different hormones, neurotransmitters, and drugs. The evolution of beta-blocker drug development has led to refinements in their pharmacodynamic actions that include agents with relative beta1-selectivity, partial agonist activity, concomitant alpha-adrenergic blockers activity, and direct vasodilator activity. In addition, long-acting and ultra-short-acting formulations of beta-blockers have also demonstrated a remarkable record of clinical safety in patients of all ages. Indeed, the beta-adrenergic blockers have provided us with a great clinical legacy for now and in years to come.