Back to Search
Start Over
β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project.
- Source :
-
Pharmacology & therapeutics [Pharmacol Ther] 2016 Mar; Vol. 159, pp. 66-82. Date of Electronic Publication: 2016 Jan 22. - Publication Year :
- 2016
-
Abstract
- 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 changing concepts of the underlying pathophysiology of the target condition while clinical development was under way; moreover, a paucity of public domain tools for the study of the drug target and aspects of receptor agonists as drugs had to be addressed. Nonetheless, a successful first-in-class launch was accomplished. Looking back at this translational pharmacology program, we conclude that a specifically tailored and highly flexible approach is required. However, several of the lessons learned may also be applicable to translational pharmacology programs in other indications.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Adrenergic beta-3 Receptor Agonists therapeutic use
Adrenergic beta-3 Receptor Antagonists pharmacology
Animals
Antibodies pharmacology
Drug Repositioning
Humans
Ligands
Receptors, Adrenergic, beta-3 genetics
Syndrome
Translational Research, Biomedical
Urinary Bladder physiology
Urinary Bladder, Overactive drug therapy
Urinary Bladder, Overactive physiopathology
Adrenergic beta-3 Receptor Agonists pharmacology
Receptors, Adrenergic, beta-3 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-016X
- Volume :
- 159
- Database :
- MEDLINE
- Journal :
- Pharmacology & therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 26808167
- Full Text :
- https://doi.org/10.1016/j.pharmthera.2016.01.007