Use of 1-pyridylamino-indole derivatives for treating stress, or mixed, urinary incontinence, activate alpha-adrenergic receptors and inhibit norepinephrine recapture

摘要

Use of 1-(pyridylamino)indole derivatives (I) for preparing a composition for treatment of stress, or mixed, urinary incontinence. 1-(Pyridylamino)indole derivatives of formula (I) and their salts are used for preparing a composition for treatment of stress, or mixed, urinary incontinence. R = hydrogen, alkyl, alkylene, alkylidyne, cycloalkyl, cycloalkylene, cycloalkylidyne, C(O)NH 2, C(O)R' or C(O)OR' (all optionally substituted and/or interrupted by O, C(O)O, OC(O), NHC(O) or C(O)NH); and R' = alkyl, alkylene, alkylidyne, cycloalkyl, cycloalkylene or cycloalkylidyne, all optionally substituted and/or interrupted as for R. [Image] ACTIVITY : Uropathic. MECHANISM OF ACTION : Activation of alpha -adrenergic receptors and selective inhibition of norepinephrine recapture. Segments of cleaned, isolated rabbit ureter were immersed in Krebs-Henseleit solution containing agents that blocked beta -adrenergic receptors, cathechol-O-methyltransferase and recapture of noradrenaline types 1 and 2, then equilibrated under a tension of 1 g. Segments that showed contractile response at least 1 g when contacted with norepinephrine (NE; 30 mu M) were then treated with indol-1-yl-pyridin-4-yl-amine salicylate. This compound induced significant contraction, e.g. when added at 10 -5 M it caused a contraction equal to about 35% of the contraction induced by a second application of NE (30 mu M).