Figure 3. Fast clearance and no brain regional specificity of (2R,6R)-HNK uptake.

Activity detected in serum and brain after bolus i.v. (1 μCi/g) administration of [³H](2R,6R)-HNK in rats (A). Saturation binding experiments using rat serum indicate the lack of high-affinity specific binding in serum proteins (B). Biodistribution of [³H](2R,6R)-HNK 30 min after IV administration, uptake was not blocked in any organ, except the liver, when pretreating the animals with 10 mg/kg of (2R,6R)-HNK (IP) (C). Lack of enrichment in any selected brain region of rats injected (i.v., 1μCi/g) with radiolabeled [³H](2R,6R)-HNK (D). Representative autoradiograms of coronal brain sections of rats injected (IV, 1μCi/g) with radiolabeled[³H](2R,6R)-HNK 30 min after i.v. administration with or without pretreatment with 10 mg/kg of (2R,6R)-HNK (IP) (E). Activity detected in plasma after bolus i.v. (100 μCi/g) administration of [³H](2R,6R)-HNK in rats (F). Whole body autoradiograms of rats injected with radiolabeled [¹⁴C](2R,6R)-HNK 30 min and 4h after bolus i.v. administration (10 mg/kg). All data points are mean ± SEM.