In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D(2)-like dopamine receptors.
Benzamide derivatives as radiotracers have played an important role in diagnosing malfunction in dopaminergic neurotransmission. A variety of halogenated and two unsubstituted benzamide derivatives were synthesised and their in vitro affinities to dopaminergic, serotonergic and adrenergic receptors and their lipophilicities were determined. As references IBZM (3), raclopride (4) and FLB457 (5) were tested as well. The two iodinated compounds NAE (27) and NADE (28) displayed K(i) values of 0.68 and 14 nM for the D(2) receptor. The well-established radiotracers FP (1) and DMFP (2) showed affinities in the same range as did the brominated compounds NABrE (29) and NABrDE (30). The log D(7.4) values of 2.91 for NAE (27) and of 2.81 for NADE (28) are in the range of those found for IBZM (3), FP (1) and DMFP (2). These facts allow to expect good properties for the two iodinated compounds NAE (27) and NADE (28) regarding in vivo imaging with SPECT.
Stark
Daniela
D
Institute of Nuclear Chemistry, Johannes Gutenberg-University, Fritz-Strassmann-Weg 2, D-55128, Mainz, Germany.
Piel
Markus
M
Hübner
Harald
H
Gmeiner
Peter
P
Gründer
Gerhard
G
Rösch
Frank
F
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry*; D002460:Cell Line; D007456:Iodine Isotopes / Q000032:analysis; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D001549:Benzamides; D007456:Iodine Isotopes; D017448:Receptors, Dopamine D2