Mirabegron (YM178) is a beta-3 adrenergic agonist that is used for treatment of overactive bladder syndrome.

β3-adrenoceptor:22.4 nM(EC50)

In anesthetized rats, intravenous injection of Mirabegron (3 mg/kg) was found to reduce the frequency of rhythmic bladder contractions without affecting the amplitude of contractions.

In CHO cells expressing human β3-adrenergic receptors, Mirabegron increases intracellular cAMP accumulation in a concentration-dependent manner. Mirabegron can induce relaxation in rat bladder smooth muscle (EC50=5.1 μM) and human bladder smooth muscle (EC50=0.78 μM) pre-treated with carbachol at concentrations of 10^-6M or 10^-7M.

Mirabegron (YM178) is dissolved in 100% DMSO and diluted with assay buffer[1]. CHO cells (105) are seeded in each well of a 24-well culture plate and subcultured. Three days later, the medium is exchanged with 250 μL/well Hanks' balanced salt solution containing 0.1 mM 3-isobutyl-1-methylxanthine, pH 7.4. The cells are incubated with each compound (isoproterenol, Mirabegron, BRL37344, and CL316,243 at final concentrations of 10-10 to 10-4 M) for 10 min at 37°C, after which incubation is stopped by the addition of 250 μL of 0.2 M HCl. cAMP concentration in the reaction mixture is measured by radioimmunoassay using an 125I-cAMP assay system using a gamma counter. Fifty microliters of reaction mixture is incubated with 50 μL of succinyl agent for 10 min at room temperature, after which the reaction is stopped by the addition of 400 μL of buffer solution. Fifty microliters of succinylated sample is incubated with 50 μL of 125I-cAMP and 50 μL of anti-cAMP antibody for 24 h at 4°C. At the end of the incubation period, 250 μL of charcoal suspension is added and centrifuged for 10 min at 2800 g at 4°C. Two hundred and fifty microliters of supernatant is transferred into a tube and counted for 1 min using a gamma counter. The intrinsic activity (I.A.) relative to isoproterenol for each β-adrenoceptor agonist is calculated using the maximal response of each compound[1].