ABSTRACT
The 5-HT(1A) receptor subtype is the most thoroughly studied serotonin receptor subtype. We report here the design, synthesis and characterization of two new fluorescent ligands for the 5-HT(1A) receptor. The new 1-arylpiperazine-based red-emitting fluorescent compound 6 displayed good binding affinity at the 5-HT(1A) receptor (K(i)=35 nM) and was able to label specifically the human 5-HT(1A) receptor stably expressed in CHO cells visualized using confocal laser scanning microscopy.
Subject(s)
Fluorescent Dyes/chemistry , Receptor, Serotonin, 5-HT1A/chemistry , Animals , CHO Cells , Cricetinae , Cricetulus , Humans , Ligands , Microscopy, Confocal , Microscopy, FluorescenceABSTRACT
A series of "long-chain" 1-(2-methoxyphenyl)piperazine derivatives containing an environment-sensitive fluorescent moiety (4-amino-1,8-naphthalimide, 4-dimethylaminophthalimide, dansyl) was synthesized. The compounds displayed very high to moderate 5-HT(1A) receptor affinity and good fluorescence properties. 6-Amino-2-[5-[4-(2-methoxyphenyl)-1-piperazinyl]pentyl]-1H-benz[de]isoquinoline-1,3(2H)-dione (4) combined very high 5-HT(1A) receptor affinity (K(i) = 0.67 nM), high fluorescence emission in CHCl(3), and undetectable fluorescence emission in aqueous solution. It was evaluated for its ability to visualize 5-HT(1A) receptors overexpressed in CHO cells by fluorescence microscopy.
