Figure 5.

Sample traces of 10 µM REL-1017 and 1 µM (±)-ketamine onset and offset kinetics. Experiments were conducted by whole-cell patch-clamp electrophysiology at a −70 mV holding potential in NR1-2C–expressing CHO cells. A protocol was established to measure how fast REL-1017 blockade of NMDAR-mediated currents can be established (onset kinetic) and how fast this blockade can be removed (offset kinetic) by perfusion with a buffer containing the agonist L-glutamate but devoid of REL-1017. Test item application protocol diagram (top) and sample traces (bottom) of test item onset and offset kinetic experiments are shown with 10 µM REL-1017-treated cell (left) or 1 µM (±)-ketamine–treated cell (right). I₀, I_1, and I₂ were the currents measured at the end of the first 5 s of 10 μM/10 μM L-glutamate/glycine application, the 30-s co-application with test item, and the final 50-s co-agonists application, respectively. In this case, s is seconds.