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Overview
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Background
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].
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