The
antispasmodic activity of
terflavoxate (CAS 86433-39-8), a
flavone derivative with
spasmolytic properties on the urinary tract, has been studied in vitro, in comparison to the most common drugs utilized in the
therapy of
overactive detrusor, namely
flavoxate,
oxybutynin, and
terodiline.
Terflavoxate showed affinity for bladder (and brain)
muscarinic receptors at micromolar level, however, its activity on
carbachol-induced contractions of rat bladder was clearly non competitive, indicating that the compound is devoid of functional
antimuscarinic property. Moreover, the observation that unlike
antimuscarinic drugs,
terflavoxate inhibited by more than 50% field stimulation-induced contractions of rabbit bladder strips, indicates that mechanisms other than the
anticholinergic one should be responsible for its smooth muscle relaxant properties.
Terflavoxate,
flavoxate,
oxybutynin, and
terodiline were equally effective in inhibiting the two components of K(+)-induced contractions, while
nifedipine and
nicardipine were more potent than the other compounds, and more effective in inhibiting tonic than phasic contractions. In addition, while
nifedipine and
nicardipine antagonized in a competitive manner
calcium-induced contractions of
potassium-depolarized bladder strips, the other
spasmolytics behaved as mixed antagonists. Differences in
calcium antagonistic properties between
nifedipine and
nicardipine on one side, and
terflavoxate on the other, are further demonstrated by the data on binding experiments. Nevertheless, present results suggest that Ca(++)-antagonistic effects are mainly responsible for
terflavoxate smooth muscle relaxant properties.