Table 1.

Relative Exchange Efflux Rate, Uptake Inhibition of [³H]-Gabapentin, and IC₅₀ Values in HEK-hLAT1 Cells for Various Natural and Non-natural, Heterocyclic, and Aromatic-Substituted Amino Acids

^aCell assay data was obtained at least in triplicate (wells) in each condition. Amino acids were either purchased (50–62, 65, 71, 85), synthesized as previously published (68–70),⁵⁶ or synthesized according to Scheme 1. All compounds above are single enantiomers of L configuration, unless indicated otherwise.

^bCompounds were tested at 200 μM for their ability to cause efflux (fmol/min) of [³H]-gabapentin from preloaded HEK-hLAT1 cells. Efflux of [³H]-gabapentin was calculated at 3 min after adding test compound. %Efflux was normalized relative to L-Phe (50), which had an efflux rate of 2.7 ± 0.3 fmol/min, from an average of seven experiments.

^cCompounds were tested at 200 μM for their ability to inhibit uptake of [³H]-gabapentin into HEIK-hLAT1 cells. Data are presented as % inhibition relative to background signal in the absence of a test compound.

^dFor IC₅₀ determinations, varying concentrations of each compound were added, from 0.1 to 500 μM. IC₅₀ and standard deviation of each compound were calculated by Graphpad Prism version 5.0. %[³H]-gabapentin uptake at each concentration was normalized relative to % inhibition by BCH^80,51 at 2 mM, which was set to 100% inhibition.