Fig. 4. Glycine concentration-dependent uptake and inhibition. (A ) Glycine uptake in untreated controls (red squares ) and effects of glycine transporter (GlyT) inhibition by ALX5407 as a specific GlyT1-inhibitor (blue circles ) and a clinically relevant combination of lidocaine and its major metabolites (green triangles ) were investigated by using mounting concentrations of extracellular glycine (12.5–100 μM). Lidocaine (4 μM) was combined with monoethylglycinexylidide (MEGX; 2.5 μM), glycinexylidide (GX; 0.3 μM), and N-ethylglycine (EG; 30 μM) to mimic clinically relevant unbound plasma concentrations after continuous systemic or epidural application of lidocaine. (B ) The degree of inhibition by ALX5407 (blue bars ) as well as by lidocaine in combination with its metabolites (green bars ) significantly decreases with increasing extracellular glycine concentrations, indicating a competitive mechanism of glycine transport inhibition. Data are presented as mean ± SD (n = 3). An asterisk indicates a significant difference between groups (P < 0.05).