Recent advances in identification and characterization of beta-adrenoceptor agonists and antagonists

The three beta-adrenoceptor subtypes (beta(1), beta(2), beta(3)) represent important therapeutic targets. The use of beta(2)-adrenoceptor agonists as bronchodilators and beta(1) or beta(1)/beta(2) antagonists as antihypertensives is well established; research is ongoing in these areas to refine pharmacodynamic properties. It is also feasible to design molecules combining beta-adrenoceptor affinity with other pharmacophores. This is facilitated by the ability to confer beta-adrenoceptor antagonist activity via attachment of a phenylethanolamine moiety or to incorporate diverse structural elements in the N-alkyl substituent of a beta-adrenoceptor agonist or antagonist. beta(3)-Adrenoceptor agonists have not yet been successfully developed as drugs for any therapeutic indication; nevertheless, during the past few years many highly potent and selective beta(3)-agonists have been reported, some with good oral bioavailability. Selective beta(3)-adrenoceptor antagonists have also been identified; useful pharmacological tools are now available for the evaluation of the functional role of each beta-adrenoceptor subtype.