Safety and tolerability of β3-adrenoceptor agonists in the treatment of overactive bladder syndrome – insight from transcriptosome and experimental studies

Abstract

ABSTRACTIntroduction: We have reviewed the safety and tolerability of β3-adrenoceptor agonists, specifically mirabegron and solabegron, a newly emerging drug class for the treatment of the overactive bladder syndrome. We discuss them mechanistically in the context of expression and other preclinical data.Areas covered: Based on a systematic PubMed search, incidence of overall adverse events, hypertension, dry mouth, and constipation are comparable between mirabegron or solabegron and placebo. Hypertension is the most frequently observed adverse event, but has a similar incidence with mirabegron and placebo. Nevertheless, severe uncontrolled hypertension has become a contraindication for use of mirabegron based on observation of severe hypertension in association with mirabegron exposure. The overall incidence of adverse events is also similar between mirabegron and the muscarinic receptor antagonist tolterodine, but the incidence of dry mouth is much lower with mirabegron.Expert opinion: The high β3-adrenoceptor mRNA expression in the human ovaries is not associated with reproductive side effects. Generally, β3-adrenoceptors exhibit a rather restricted expression in human tissues, which may explain the overall good tolerability of agonists acting on this receptor. We propose that expression profiles and functional preclinical studies can be important tools in the prediction of adverse event profiles in first-in-class drugs.