Saturable transport of the neurokinin-1 non-peptide antagonist LY303870 across the rat blood-brain barrier after intravenous administration

LY303870 (LY) is a non-peptide neurokinin-1 receptor antagonist that has ef fects on the brain after peripheral administration. We determined whether L Y given by intravenous (iv) injection can cross the blood-brain barrier (BB B). Multiple-time regression analysis showed the unidirectional influx rate (Ki) from blood to brain for LY labeled with tritium to be 6.41 +/- 0.85 m ul/g-min and influx was inhibited by unlabeled LY. HPLC and mass spectromet ry showed LY was stable in blood and brain. LY reached a brain/serum ratio of 190 +/- 12 mul/g with about 0.07% of the injected dose entering each gra m of brain. These results show that LY is transported across the BBB from s erum into brain by a saturable system. (C) 2001 Elsevier Science Inc. All r ights reserved.