Search results for "Adrenergic beta-3 Receptor Antagonists"
showing 3 items of 3 documents
The Odd Sibling: Features ofβ3-Adrenoceptor Pharmacology
2014
beta(3)-Adrenoceptor agonists have recently been introduced for the treatment of overactive urinary bladder syndrome. Their target, the beta(3)-adrenoceptor, was discovered much later than beta(1)- and beta(2)-adrenoceptors and exhibits unique properties which make extrapolation of findings from the other two subtypes difficult and the beta(3)-adrenoceptor a less-understood subtype. This article discusses three aspects of beta(3)-adrenoceptor pharmacology. First, the ligand-recognition profile of beta(3)-adrenoceptors differs considerably from that of the other two subtypes, i.e., many antagonists considered as nonselective actually are beta(3)-sparing, including propranolol or nadolol. Man…
The new radioligand [H-3]-L 748,337 differentially labels human and rat beta(3)-adrenoceptors
2013
As no suitable radioligand exists for the detection of β3-adrenoceptors, we have explored the radioligand binding properties of a tritiated version of the selective β3-adrenoceptor antagonist L 748,337. Kinetic and equilibrium saturation and competition binding experiments were performed with [(3)H]-L 748,337 on membrane fractions of HEK and CHO cells stably transfected with human and rat β-adrenoceptor subtypes. Based on both association/dissociation kinetic and equilibrium saturation binding studies in transfected HEK cells, [(3)H]-L 748,337 exhibited an affinity of approximately 2 nM for human β3-adrenoceptors. Competition studies with agonists and subtype-selective antagonists validated…
β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project
2016
β3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the β3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changin…