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In Vitro
Journal Article
Effects of terflavoxate on stimulated contractions of urinary bladder in vitro.
Arzneimittel-Forschung 1993 Februrary
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.
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