title: Therapeutic potential of functional selectivity in the treatment of heart failure.
abstract: Adrenergic and angiotensin receptors are prominent targets in pharmacological alleviation of cardiac remodeling and heart failure, but their use is associated with cardiodepressant side effects. Recent advances in our understanding of seven transmembrane receptor signaling show that it is possible to design ligands with "functional selectivity," acting as agonists on certain signaling pathways while antagonizing others. This represents a major pharmaceutical opportunity to separate desired from adverse effects governed by the same receptor. Accordingly, functionally selective ligands are currently pursued as next-generation drugs for superior treatment of heart failure.
authors.affiliation: Department of Clinical Biochemistry, Glostrup Research Institute, Glostrup Hospital, DK-2600 Glostrup, Denmark.
authors.forename: Gitte Lund
authors.initials: GL
authors.lastname: Christensen
authors.forename: Mark
authors.initials: M
authors.lastname: Aplin
authors.forename: Jakob Lerche
authors.initials: JL
authors.lastname: Hansen
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D011943:Receptors, Adrenergic, beta