Current and emerging pharmacological targets for medical expulsive therapy

The primary goals of medical expulsive therapy are to increase the rate of stone expulsion along the ureter to avoid ureteral obstruction and reduce ureteral colic, and thus avoid the need for surgical and more invasive interventions. This review focuses on the findings from in vivo and in vitro animal and human studies that have investigated the pharmacological mechanisms controlling ureteral motility and their translation to current and potentially new clinically used drugs for increasing rate of stone expulsion along the ureter. The complicated contractility profile of the ureter, which alters with age, tissue segment region, orientation, and species, contributes to the difficulty of interpreting studies on ureteral pharmacology, which translates to the complexity of discovering ideal drug targets for medical expulsive therapy. Nevertheless, the current drug classes clinically used for patients with stone lodgement include α1-adrenoceptor antagonists, calcium channel blockers and NSAIDS, while there are promising targets for drug development that require further clinical investigations including the phosphodiesterase type 5 enzyme, β-adrenoceptors and 5-HT receptors.