Background:

Mirabegron is a selective β3-adrenoceptor agonist with EC50 of 22.4 nM.

Mirabegron (YM178) increases cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human β3-adrenoceptor (AR). EC50 value is 22.4 nM. EC50 values of Mirabegron for human β1- and β2-ARs are 10,000 nM or more, respectively. EC50 of Mirabegron in rat bladder strips precontracted with 10-6 M Carbachol (CCh) is 5.1 μM, whereas that in human bladder strips precontracted with 10-7 M CCh is 0.78 μM. Mirabegron concentration-dependently increases the accumulation of cAMP in CHO cells expressing human β3-ARs, with an EC50 value and I.A. of 22.4 nM and 0.8, respectively. Mirabegron has little agonistic effect on β1- and β2-ARs. Compared by EC50 value, Mirabegron is approximately one third as potent as isoproterenol. The maximal relaxant effects of Mirabegron are 94±1%, that of CCh, indicating that Mirabegron acts a full agonist in the rat bladder. The maximal relaxant effects of Mirabegron is 89.4±2.3%[1].

Mirabegron (YM178) produces a dose-dependent decrease in the frequency of rhythmic bladder contraction in anesthetized rats. In contrast, Mirabegron does not decrease the amplitude of rhythmic bladder contraction at up to 3 mg/kg i.v.. On the contrary, Oxybutynin significantly increases the frequency of rhythmic bladder contraction and decreased its amplitude at doses of 0.272 mg/kg i.v. or more[1].

参考文献:
[1]. Takasu T, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007 May;321(2):642-7.