Mirabegron (YM178)

Mirabegron (YM178) is the first selective β₃-adrenoceptor (β₃-AR) agonist with EC50 value of 22.4 nM which is clinically effective for overactive bladder [1].

β₃-AR, one of three β-adrenoceptors (β-AR) subtypes, is sparsely distributed in the humans, and functional responses regulated by have been discovered in human brown and white fat cells, and gall bladder, stomach, small intestine, prostate, colon, and bladder [1].

Mirabegron (YM178) exhibits significant selectivity for β-ARs. When tested with Chinese hamster ovary expressing human β-ARs, EC50 values of Mirabegron for β₁-ARs, β₂-ARs and β₃-ARs were 22.4 nM, 10000 nM or more, respectively. The ratio of intrinsic activities of Mirabegron (YM178) versus maximal response induced by isoproterenol of nonselective β-AR agonist was 0.8 for human β₃-AR, 0.1 for human β₁-AR, and 0.1 for human β₂-AR [1].

In anesthetized rats, Mirabegron (YM178) at a dose of 3 mg/kg i.v. reduced the frequency of rhythmic bladder contraction caused by intravesical filling with saline without inhibiting its amplitude. By contrast, Oxybutynin apparently raised the frequency of rhythmic bladder contraction and reduced its amplitude at doses of 0.272 mg/kg i.v. or more [1].

Reference

[1]. Takasu T, Ukai M, Sato S, 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. The Jounal of pharmacology and experimental therapeutic. 2007, 321(2):642-7.