The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder

Inhibition of cholinergic neurotransmission by β3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders

“…Stimulation of ␤ 3 -adrenoceptors reduces basal bladder tension (decreasing spontaneous microcontractions in vitro and nonvoiding contractions in vivo) and relaxes bladder strips precontracted with carbachol or KCl (30,59,70). Whether the direct relaxant effect of ␤ 3 -adrenoceptor agonists on detrusor smooth muscle is the primary underlying mechanism to improve OAB symptoms has increasingly been questioned (22,28,49). The key argument is that the peak plasma levels of mirabegron when administered in therapeutic (50 mg daily) doses (83-167 nM) are below its potency (EC 50~1 -3 M) to relax detrusor smooth muscle strips (reviewed in 40).…”