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.
Hieble
J Paul
JP
Dept of Urogenital Pharmacology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania, 19406-0939, USA. j_paul_hieble@gsk.com
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000145:classification*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta