A Positive Modulator of KCa2 and KCa3 Channels, 4,5-Dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), Inhibits Bladder Afferent Firing in Vitro and Bladder Overactivity in Vivo

Sep 30, 2008The Journal of pharmacology and experimental therapeutics

A compound that enhances specific potassium channels reduces bladder nerve activity and overactive bladder symptoms

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Abstract

NS4591 at 45 ± 6 nM doubled IK-mediated currents in bladder cells.

  • A novel modulator, NS4591, was characterized for its effects on calcium-activated potassium channels.
  • At a concentration of 10 µM, NS4591 reduced the number of action potentials in bladder neurons.
  • NS4591 decreased muscle contractions in rat bladder tissues caused by carbachol in an apamin-sensitive manner.
  • In vivo, NS4591 at 30 mg/kg inhibited bladder overactivity in both rat and cat models.

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