The effects of flavoxate hydrochloride on voltage‐dependent L‐type Ca 2+ currents in human urinary bladder

The effects of flavoxate hydrochloride (Bladderon®, piperidinoethyl‐3‐methylflavone‐8‐carboxylate; hereafter referred as flavoxate) on voltage‐dependent nifedipine‐sensitive inward Ba 2+ currents in human detrusor myocytes were investigated using a conventional whole‐cell patch‐clamp. Tension measurement was also performed to study the effects of flavoxate on K + ‐induced contraction in human urinary bladder. Flavoxate caused a concentration‐dependent reduction of the K + ‐induced contraction of human urinary bladder. In human detrusor myocytes, flavoxate inhibited the peak amplitude of voltage‐dependent nifedipine‐sensitive inward Ba 2+ currents in a voltage‐ and concentration‐dependent manner ( K i =10  μ M ), and shifted the steady‐state inactivation curve of Ba 2+ currents to the left at a holding potential of −90 mV. Immunohistochemical studies indicated the presence of the α 1C subunit protein, which is a constituent of human L‐type Ca 2+ channels (Ca V 1.2), in the bundles of human detrusor smooth muscle. These results suggest that flavoxate caused muscle relaxation through the inhibition of L‐type Ca 2+ channels in human detrusor.British Journal of Pharmacology (2005) 146 , 25–32. doi: 10.1038/sj.bjp.0706284