4,5,9,10-Tetrahydro-1,4-ethanobenz[b]quinolizine as a prodrug for its quinolizinium cation as a ligand to the open state of the TCP-binding site of NMDA receptors.
A new derivative of 4,5,9,10-tetrahydro-1,4-ethanobenz[b]quinolizine (2) has been designed as a prodrug for its quinolizinium cation (1) that is a potent antagonist of the TCP-binding site of NMDA receptors at the open state. The 11C-labeled 2 showed high accumulation of radioactivity in the brain in an in vivo biodistribution study. The speculation of 2 as a prodrug of 1 has been proven by the fact that 1 was observed in a high ratio to 2 in an analysis by RP-HPLC of the brain homogenates.
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
S
S
Sasaki
T
T
Kanda
N
N
Ishibashi
F
F
Yamamoto
T
T
Haradahira
T
T
Okauchi
J
J
Meda
K
K
Suzuki
M
M
Maeda
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008024:Ligands; D051379:Mice; D011355:Prodrugs / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014018:Tissue Distribution
C425122:4,5,9,10-tetrahydro-1,4-ethanobenz(b)quinolizine; D008024:Ligands; D011355:Prodrugs; D011804:Quinolines; D016194:Receptors, N-Methyl-D-Aspartate