bèta3agonisten

Beta-3 adrenergic receptor agonists are a class of sympathomimetic medicines that selectively stimulate β3-adrenergic receptors. These receptors are primarily expressed in bladder detrusor muscle and in adipose tissue, with less pronounced effects in other smooth muscles and metabolic tissues. By selectively targeting β3 receptors, these drugs aim to produce therapeutic effects with a lower risk of cardiovascular side effects associated with β1 and β2 stimulation.

Mechanism and effects: Activation of β3 receptors increases cyclic AMP via Gs proteins, leading to relaxation of detrusor smooth muscle during the storage phase of the bladder. This results in increased bladder capacity and reduced urinary urgency and frequency in conditions such as overactive bladder. In adipose tissue, β3 stimulation can promote lipolysis, though this metabolic effect is of limited therapeutic relevance in routine clinical use.

Clinical use: The principal indication for β3-adrenergic agonists is overactive bladder. Mirabegron is the first-in-class selective β3-AR agonist, used as monotherapy or in combination with antimuscarinics. A second agent, vibegron, has been developed and approved in various regions for similar indications. Typical dosing aims to balance efficacy in reducing urgency with tolerability and blood pressure considerations.

Adverse effects and safety: Common adverse effects include hypertension, tachycardia, headache, and urinary tract infections. Because mirabegron can inhibit CYP2D6, it may increase plasma levels of drugs metabolized by this enzyme, necessitating cautious use with certain medications. β3 agonists are generally preferred when antimuscarinic therapy is poorly tolerated due to fewer anticholinergic adverse effects, though they may not address all symptoms in every patient.

Overview: β3-adrenergic receptor agonists offer a targeted option for overactive bladder management, providing symptom relief with a distinct safety profile compared to non-selective beta-agonists. Further development continues to expand indications and optimize tolerability.