Abstract
Introduction: Stimulation of the β3-adrenoceptor (β3-AR) is thought to be a valuable approach for the treatment of obesity, type 2 diabetes, heart failure, frequent urination, preterm labor, anxiety and depression. Therefore, the β3-AR is recognized as an attractive target for drug discovery. Simultaneous activation of the β1- and β2-AR can cause undesirable side effects such as increased heart rate and muscle tremors. Consequently, much effort has been directed towards the design and development of selective β3-AR agonists through original synthetic chemistry, extensive in vitro tests and detailed preclinical investigations to various phases of clinical trials.
Areas covered: SciFinder Scholar, PubMed, ISI web of KnowledgeSM, Espacenet, ClinicalTrials and Google have been used as the main sources for retrieving literature and patents filed since the discovery of β3-AR through to June 2010. This review discusses the enormous efforts made by private and public research laboratories to uncover β3-AR ligands and to prove their usefulness as drugs.
Expert opinion: Remarkable knowledge has been gained about the physio-pathological role of the β3-AR to date. Many highly potent and selective β3-AR ligands (agonists, antagonists and inverse agonists) have been discovered; however, further investigations are still needed to identify novel compounds acting as β3-AR ligands in order to adequately treat the diseases in which β3-AR is involved.