Mirabegron

Mirabegron is a small synthetic molecule that activates the beta-3 adrenergic receptor. Its first published pharmacology, from a pharmaceutical research team in Japan in 2007, described it under the development code YM178 as a selective beta-3 agonist that relaxed rat and human bladder strips (Takasu et al., 2007).

PubChem CID 9865528 lists the same formula, weight and CAS number and is the source of the aliases, IUPAC name and structure.

This page summarizes six areas of mirabegron research, each with its model. Several findings conflict.

Receptor selectivity in cell and tissue models

In Chinese hamster ovary (CHO) cells expressing human beta receptors, YM178 raised cyclic AMP with an EC50 of 22.4 nM at beta-3, against 10,000 nM or more at beta-1 and beta-2 (Takasu et al., 2007).

In rodent smooth muscle and in cells expressing human alpha-1 receptors, however, mirabegron acted as a competitive alpha-1A and alpha-1D antagonist at micromolar concentrations, but not at alpha-1B (Alexandre et al., 2016). In isolated mouse and guinea pig atria it raised beating rate, an effect the authors traced mainly to beta-1 receptors (Noguchi et al., 2026). Models: recombinant cell lines and isolated rodent tissue.

Bladder and urethral smooth muscle

Mirabegron relaxed carbachol-precontracted rat and human bladder strips (EC50 5.1 and 0.78 µM), and 3 mg/kg given intravenously to anesthetized rats lowered the frequency of rhythmic bladder contractions without reducing their amplitude (Takasu et al., 2007). In mouse urethra, the beta-3 antagonist L-748,337 shifted its relaxation curve, beta-1 and beta-2 antagonists did not, and cAMP rose (Alexandre et al., 2016).

In human detrusor tissue from cystectomy, it inhibited nerve-evoked contractions at 10 µM but not 1 µM, and L-748,337 did not block this; the authors called the effect off-target, needing concentrations far above reported plasma levels (Huang et al., 2022). Models: rodent and human tissue, anesthetized rats.

Brown adipose tissue in human studies

In 12 healthy men, mirabegron raised brown adipose tissue (BAT) metabolic activity on 18F-FDG PET/CT compared with placebo in every participant, and resting metabolic rate rose about 13% (Cypess et al., 2015). In a later study, 12 healthy men each received placebo and two single amounts on separate visits: BAT activity rose more than proportionally with amount, only the higher amount raised nonesterified fatty acids and resting energy expenditure, and gallbladder size increased (Baskin et al., 2018).

In an open-label study of 14 healthy women given mirabegron for 4 weeks, BAT activity, resting energy expenditure, HDL and insulin sensitivity were higher, with no change in body weight or composition (O'Mara et al., 2020). All three were small and short. Another human study found BAT thermogenesis rose only at the highest amount studied, where off-target beta-1 and beta-2 binding raised cardiovascular responses and white fat lipolysis (Blondin et al., 2020).

Adipocytes and white fat browning in cell and mouse models

Cell studies disagree on the receptor in human brown fat. In cultured human brown adipocytes, beta-2 stimulation and inhibition, plus knockdown of each beta receptor, pointed to beta-2 signaling for lipolysis and thermogenesis (Blondin et al., 2020). In human brown/beige adipocytes from neck fat, silencing the beta-3 receptor abolished mirabegron-stimulated lipolysis and thermogenesis (Cero et al., 2021).

In mouse brown and brite (beige) adipocytes, mirabegron raised cAMP, UCP1 mRNA and glucose uptake, effects largely absent in cells from beta-3 receptor knockout mice; in mice, its effects on oxygen consumption and glucose uptake into brown and inguinal white fat also required the beta-3 receptor (Dehvari et al., 2020). White fat browning was also reported in ApoE and LDL receptor knockout mice (Sui et al., 2019) and in APOE*3-Leiden.CETP mice (Ying et al., 2023).

Heart failure trials and atherosclerosis models

In a placebo-controlled trial in 70 people with chronic heart failure, the 6-month change in left ventricular ejection fraction (LVEF, the primary endpoint) did not differ from placebo; an exploratory subgroup analysis reported an increase (Bundgaard et al., 2017). In a similar trial in 296 people with left ventricular hypertrophy, effects on LV mass and diastolic function over 12 months were neutral (Balligand et al., 2023).

Mouse atherosclerosis findings conflict. In ApoE and LDL receptor knockout mice, mirabegron accelerated plaque growth and instability through thermogenesis-driven lipolysis that raised LDL and VLDL remnant cholesterol; deleting UCP1 abolished it (Sui et al., 2019). In APOE*3-Leiden.CETP mice, which keep a working ApoE-LDLR clearance pathway, it did not worsen atherosclerosis (Ying et al., 2023).

Reported adverse findings

In 17 healthy adults given four ascending single amounts, systolic blood pressure rose more at the two highest amounts, and heart rate more at the highest, than at the lowest of the four amounts (Loh et al., 2019).

In accidental dog exposures reported to an animal poison control center, tachycardia and erythema were the most common signs, many dogs showed none, and none died; the authors note high toxicity risk in dogs in preclinical studies (Schmid and Hovda, 2018).