The inhibitory effects of
NS-21, a newly developed
drug for the treatment of urinary frequency and
urinary incontinence, and its active metabolite,
RCC-36, on L-type Ca2+ currents (ICa) in guinea pig detrusor smooth muscle cells have been compared to those of
terodiline by a whole-cell patch-clamp technique. Like
terodiline (10 microM), both
NS-21 (10 microM) and
RCC-36 (10 microM) induced a sizeable decrease in ICa elicited from a holding potential of -60 mV without changing the current-voltage relationship. The three drugs shifted the inactivation curves for ICa in the hyperpolarizing direction by 13 to 20 mV but had no effect on the activation curves for ICa resulting in a decrease in the
calcium window current. The inhibitory effects of
NS-21 and
RCC-36 were greater than those of
terodiline. The three drugs inhibited ICa in a concentration- and holding-potential-dependent manner. The IC50 values at a holding potential of -60 mV were 7.9 microM for
NS-21, 6.4 microM for
RCC-36, and 5.9 microM for
terodiline, and at -40 mV they were 1.3, 1.2, and 3.5 microM, respectively. The ratio calculated by dividing the IC50 value at -60 mV by the value at -40 mV was 6.1, 5.3 and 1.7, respectively, indicating that the inhibitory effects of
NS-21 and
RCC-36 on ICa were more sensitive to voltage than those of
terodiline. These results suggest that
NS-21 and
RCC-36 could be more effective in the treatment of urinary bladder ailments, such as urinary frequency and
urinary incontinence.