Figure 5.

Pharmacokinetic model of ((2S, 3R)‐3‐hydroxy‐2‐((R)‐5‐isobutyryl‐1‐oxo‐2,5‐diazaspiro[3,4]octan‐2‐yl) butanamide (NYX‐2925)‐mediated metaplasticity. Cartoon depicting absorption, metabolism, and elimination of NYX‐2925. Following an oral drug bolus, central levels of NYX‐2925 raise into the concentration range (~44 nanomolar within ~1 h) that facilitates LTP in vivo (Khan et al. 2018). With time (> 8 h), drug concentrations fall into the range where homeostatic plasticity is observed (low picomolar), which may account for both the rapid and long‐lasting effects of drug seen in vivo following a single treatment. Thus, at some point, brain NYX‐2925 concentrations fall within both the ionotropic and putative metabotropic ranges after oral dosing.