Off-Target Effects of Mirabegron on Muscarinic Receptors

Older adults with multiple diseases are likely to be prescribed multiple medications including anticholinergic agents, which are frequently prescribed to manage conditions such as overactive bladder and chronic obstructive pulmonary disease and Parkinson’s disease. Overactive bladder (OAB) has been the subject of increased disease awareness and is a common and significant cause of reduced quality of life, particularly in the elderly. The selective β₃ adrenoceptor agonist, mirabegron was developed for the pharmacological treatment of OAB. Mirabegron has been shown to exert off-target effects on various functional proteins such as muscarinic receptors in rat tissues. This agent may relax the detrusor muscle by activating β₃ adrenoceptors and also antagonizing muscarinic receptors. Mirabegron and antimuscarinics exerted additive effects on muscarinic receptor binding and relaxant responses of cholinergic contractions of the detrusor muscle. Mirabegron excreted in human urine appears to directly attenuate muscarinic receptor-mediated functions in the bladder. Combination therapy of mirabegron and solifenacin in patients with OAB may enhance not only their therapeutic effects on OAB, but also increase the risk of anticholinergic adverse effects. Therefore, the safety of concomitant use of mirabegron and other drugs such as antimuscarinics for elderly patients needs to be carefully considered.