TY - JOUR
T1 - A prodrug of NMDA/Glycine site antagonist, L-703,717, with improved BBB permeability
T2 - 4-Acetoxy derivative and its positron-emitter labeled analog
AU - Haradahira, T.
AU - Zhang, M. R.
AU - Maeda, J.
AU - Okauchi, T.
AU - Kida, T.
AU - Kawabe, K.
AU - Sasaki, S.
AU - Suhara, T.
AU - Suzuki, K.
PY - 2001
Y1 - 2001
N2 - 4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.
AB - 4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.
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U2 - 10.1248/cpb.49.147
DO - 10.1248/cpb.49.147
M3 - Article
C2 - 11217099
AN - SCOPUS:0035114794
SN - 0009-2363
VL - 49
SP - 147
EP - 150
JO - Chemical and Pharmaceutical Bulletin
JF - Chemical and Pharmaceutical Bulletin
IS - 2
ER -