Albumin binding and brain uptake of 6-fluoro- dl-tryptophan: competition with l-tryptophan

We investigated potential competition between l-tryptophan (TRP) and 6-fluoro- dl-tryptophan (6-F-TRP) for binding to albumin and for passage through the blood-brain barrier (BBB). In experiments based on equilibrium dialysis, albumin (600 μM) bound about 80% of TRP and 50% of 6-F-TRP with affinity constants ( K a ) of 3.7 ± 0.04 × 10 4 and 0.62 ± 0.01 × 10 4 M −1, respectively. Competitive inhibition was assessed as the decrease in the apparent K a ( K a ) of TRP in the presence of 6-F-TRP, with no modification of the N value. Competition between TRP, 6-F-TRP and l-valine (VAL) for passage across the BBB was demonstrated using two approaches. When administered concomitantly with TRP or 6-F-TRP to rats, VAL decreased brain uptake of TRP and 6-F-TRP and reversed their action on serotonin. In Oldendorf's model, 6-F-TRP and VAL decreased the brain uptake of TRP.