ALTERATIONS IN K-EVOKED RELEASE OF H-3 NOREPINEPHRINE AND CONTRACTILERESPONSES IN URETHRAL AND BLADDER TISSUES INDUCED BY NOREPINEPHRINE REUPTAKE INHIBITION()
Mm. Foreman et Am. Mcnulty, ALTERATIONS IN K-EVOKED RELEASE OF H-3 NOREPINEPHRINE AND CONTRACTILERESPONSES IN URETHRAL AND BLADDER TISSUES INDUCED BY NOREPINEPHRINE REUPTAKE INHIBITION(), Life sciences, 53(3), 1993, pp. 193-200
The effects of norepinephrine (NE) reuptake inhibition on NE release a
nd contractile responses in lower urinary tract tissues were evaluated
using tomoxetine, a selective NE reuptake inhibitor, and imipramine,
a nonselective reuptake inhibitor. Although both compounds significant
ly increased K+-evoked release of NE from urethral fragments obtained
from rabbits, tomoxetine was at least 10X more potent than imipramine.
Tomoxetine significantly enhanced the effects of NE to contract rabbi
t urethral fragments and to relax carbachol contracted rabbit bladder
smooth muscle. Imipramine suppressed the effects of NE on urethral tis
sue and was less potent than tomoxetine in enhancing bladder responses
to NE. These presynaptic and postsynaptic effects of NE reuptake inhi
bition in lower urinary tract tissues may contribute to the efficacy o
f imipramine in treating incontinence and represent a new clinical uti
lity for selective and more potent reuptake inhibitors, such as tomoxe
tine.