in rats: maximal electroshock (MES) and the PTZ anticonvulsant assays: MES ED50 = 1.5 mg/kg, PTZ ED50 = 2.2 mg/kg

It was measured the effects of ICA-069673 on global intracellular Ca2+ levels in detrusor smooth muscle (DSM) single cells. For the control, the average emitted intensity (F340/F380) prior to ICA-069673 application was 0.470 ± 0.006 (n = 11, N = 5). At 10 μM ICA-069673, there was a significant decrease in the F340/F380 ratio to 0.450 ± 0.006 (n = 11, N = 5; P < 0.001). To elucidate the mechanism by which ICA-069673 regulates global intracellular Ca2+ concentrations, it was studied the effects of ICA-069673 (10 µM) in the presence or absence of the L-type CaV channel blocker nifedipine (1 µM). In the presence of 1 µM nifedipine, ICA-069673 (10 µM) had no significant effect on global intracellular Ca2+ levels, with the average F340/F380 ratio being 0.470 ± 0.008 compared with the control value of 0.480 ± 0.005 (n = 11, N = 5; P > 0.05). These results demonstrate that in DSM cells, ICA-069673 decreases global intracellular Ca2+ concentrations by an indirect mechanism involving inhibition of Ca2+influx through L-type CaV channels, probably as a result of membrane hyperpolarization.