, Volume 386, Issue 3, pp 247-253
Date: 14 Dec 2012

In vitro and in vivo pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in rats

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To investigate the pharmacological properties of mirabegron in in vitro and in vivo, the effects on cAMP accumulation in Chinese hamster ovary (CHO) cells expressing rat β-adrenoceptors, the relaxant activity in isolated rat bladder smooth muscle, and the voiding effects in cerebral infarcted rats were evaluated. Mirabegron increased cAMP accumulation with EC50 value and intrinsic activity of 19 nmol/L and 1.0, respectively, in CHO cells expressing rat β3-adrenoceptors. The EC50 values and the intrinsic activities of mirabegron were 610 nmol/L and 0.6 for rat β1-adrenoceptors and were sumless and 0.1 for β2-adrenoceptors, respectively. Mirabegron showed concentration-dependent relaxant and full agonistic effects in rat bladder strips under passive tension with EC50 value of 290 nmol/L. The concentration–response curve of mirabegron was affected neither by the β1-adrenoceptor selective antagonist CGP-20712A nor by the β2-adrenoceptor selective antagonist ICI-118,551. In in vivo studies with cerebral infarcted rats, a significant decrease in the volume voided per micturition compared with sham-operated rats was observed. Mirabegron dose-dependently increased the volume voided per micturition. In conclusion, we have extended the selectivity profile of mirabegron to rats and demonstrated that it is effective via stimulation of β3-adrenoceptors in a rat cerebral infarction model of detrusor overactivity.