Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat.

摘要: Because all three components of lower urinary tract control (parasympathetic, sympathetic and somatic) are intimately associated with serotonin (5-hydroxytryptamine [5HT])- norepinephrine (NE)- containing terminals receptors, in the present study, we examined effects increasing extracellular levels 5HT NE duloxetine, a reuptake inhibitor, on function under "normal" or nonirritated conditions (transvesical infusion saline) model bladder irritation (i.e., transvesical 0.5% acetic acid) chloralose-anesthetized cats. Irritation reduced capacity (to 20% control) produced insignificant increases periurethral electromyographic (EMG) activity compared animals. Duloxetine sphincter EMG when administered conditions. However, this duloxetine "pretreatment" did prevent typical acid-induced reductions unmasked marked activation acid (by 8-fold). Furthermore, initially irritated conditions, dose-dependent 5-fold) increased striated muscle The were due to central mechanisms since contractions evoked by direct electrical stimulation efferent fibers pelvic nerve not effected duloxetine. antagonized methiothepin, non-selective receptor antagonist, but other antagonists examined: LY53857, 5HT2 antagonist; prazosin, an alpha-1-adrenergic idazoxan, alpha-2-adrenergic propranolol, beta-adrenergic antagonist. facilitatory significantly various degrees LY53857 prazosin idazoxan propranolol. These results indicate that through inhibition reuptake, has weak normal irritation, suppresses enhances external urethral mechanisms.