β3-adrenoceptor agonists are currently in clinical development for the treatment of overactive bladder and considered for several other indications. This Perspective discusses desirable properties of such drugs mainly based on the example of overactive bladder, but at least partly they should also be applicable to other indications of β(3)-adrenoceptor agonists or other drug classes and therapeutic areas. These include degree of selectivity for the molecular target in terms of affinity, intrinsic efficacy and ligand-directed signaling. The ability to cause agonist-induced desensitization and the potential impact of gene polymorphisms also need to be considered. Depending on intended indication, specific pharmacokinetic considerations may also apply. These findings challenge the usefulness of high-throughput screening assays based upon a single molecular response in an artificial system and emphasize the need for early use of in vivo testing in species considered to be predictive for the human situation.
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