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 effects on the brain after peripheral administration. We determined whether LY given by intravenous (iv) injection can cross the blood-brain barrier (BBB). 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 microl/g-min and influx was inhibited by unlabeled LY. HPLC and mass spectrometry showed LY was stable in blood and brain. LY reached a brain/serum ratio of 190+/-12 microl/g with about 0.07% of the injected dose entering each gram of brain. These results show that LY is transported across the BBB from serum into brain by a saturable system.
Banks
W A
WA
GRECC, Veterans Affairs Medical Center-St. Louis, Department of Internal Medicine, Saint Louis University School of Medicine, MO 63106, USA. bankswa@slu.edu
McMillian
C L
CL
Iyengar
S
S
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats
C096759:1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines