F-18 LABELED BENZAMIDES FOR STUDYING THE DOPAMINE-D(2) RECEPTOR WITH POSITRON EMISSION TOMOGRAPHY

被引:58
作者
MACH, RH
LUEDTKE, RR
UNSWORTH, CD
BOUNDY, VA
NOWAK, PA
SCRIPKO, JG
ELDER, ST
JACKSON, JR
HOFFMAN, PL
EVORA, PH
RAO, AV
MOLINOFF, PB
CHILDERS, SR
EHRENKAUFER, RL
机构
[1] UNIV PENN,CEREBROVASC RES CTR,PHILADELPHIA,PA 19104
[2] UNIV PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19104
[3] WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,WINSTON SALEM,NC 27157
关键词
D O I
10.1021/jm00075a028
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan-3beta-yl)benzamides were prepared, and in vitro binding assays were used to measure the affinity of these compounds for dopamine D2, dopamine D3, serotonin 5-HT2, and alpha2-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors. F-18-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation of the corresponding desbenzyl precursors with [F-18]-4-fluorobenzyl iodide. Preliminary in vivo studies demonstrated that [F-18]-23 and [F-18]-26b are suitable candidates for further evaluation in positron emission tomography imaging studies. The slow rate of washout of [F-18]-34 from nondopaminergic regions and its comparatively high lipophilicity indicates that this compound may not be suitable for imaging studies because of a high level of nonspecific binding.
引用
收藏
页码:3707 / 3720
页数:14
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