Table 3

Mean CSF and plasma levels following 2-min intravenous bolus of 2.8 mg/kg Ro 63-1908 followed by 1-h infusion of 5.6 mg/kg/h to rats (n = 2 rats/time point) of pre-Ro 63-1908 control, n = 7). Representative recordings are shown. Applications of drugs are indicated by bars. B, comparison of the kinetics and extent of inhibition of steady-state inward currents elicited by either 10 or 100 μM NMDA after fast application of Ro 63-1908. Single exponential curves were fitted to the digitized data that yielded mean on-rate time constants of 2663 ± 146 ms (n = 8) and 1022 ± 50 ms (n = 8) for the block of the steady-state currents elicited by 10 and 100 μM NMDA, respectively. Application of Ro 63-1908 resulted in 62 ± 2% and 90 ± 2% inhibition of steady-state currents elicited by 10 and 100 μM NMDA, respectively. Ro 63-1908 showed a faster onset and higher efficacy of NMDA receptor blockade at the higher level of NMDA receptor activation (P < 0.0001, two-tailed t test). Representative current recordings are shown. Current amplitudes were normalized to facilitate comparison.