Coadministration of low-dose serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine with α 2-adrenoceptor blockers to treat both female and male mild-to-moderate stress urinary incontinence (SUI)
Background. Female urinary incontinence is a relatively common disorder affecting women in different age groups, with significant prevalence amounts of stress-related subtype (stress urinary incontinence, SUI). Various neurotransmitters/neuromodulators - particularly both the glutamatergic and GABA-ergic ones - are involved in micturition/urinary continence nerve centre-based control, where Onuf's nucleus plays an important functional role under the adiuvant serotoninergic/ noradrenergic influences.
Objectives. To outline, deriving them from the literature review, the SUI therapeutic implications of SNRI (serotonin-noradrenaline reuptake inhibitors) particularly of the duloxetine, though displaying its full therapeutic dose (40 mg twice/day)-related side effects and, therefore, highlighting recent issues concerning novel drug administration modalities to avoid such adverse events.
Emerging knowledges. Intriguing studies in SUI animal models have shown that co-administration of duloxetine low dose with α 2-adrenoceptor antagonists - given the α 2-adrenoceptor inhibition-induced enhancement of duloxetine effectiveness on the urethral rhabdospincter-can avoid the duloxetine-related adverse events though perspectively reaching, in perspective translational clinical applications, the awaited beneficial effects for women suffering from intrinsic rhabdosphincter deficiency-based mild-to-moderate SUI as well as, in men, to treat post-prostatectomy mild SUI.
