Selective Dopamine D-1 and D-2 Fluorescent Probes.

摘要

The objective of Phase I was to develop fluorescent probes for dopamine receptors. Researchers resolved the R- and S-enantiomers of PPHT, developed synthetic routes for amine derivatives of RS-, R-, and S-PPHT (D2 dopamine receptor agonists) and RS-SKF 38393 (a selective D1 dopamine receptor agonist), and optimized the experimental conditions for coupling of these precursors with commercially available amine-selective fluorescent tags, fluorescein isothiocyanate and NBD-chloride. Several fluorescent compounds prepared for the study retained high affinity for D2 dopamine receptors and high receptor selectivity. The NBD derivative of S-PPHT exhibited increased affinity for D2 dopamine receptors and increased D2/D1 dopamine receptor selectivity (200 fold) compared to the parent compound. The fluorescent drugs bound to slide-mounted brain tissue and were detectable under fluorescence microscope.