New 5-HT1A receptor antagonist: [H-3]p-MPPF

A new 5-HT1A receptor antagonist ligand, [H-3]p-MPPF, 4-(2'-methoxy-)-phenyl-1-[2'-(N-2 ''-pyridyl)-p-fluorobenzamido]ethyl-piperazine, was prepared and characterized. It demonstrated high affinity and selectivity toward 5-HT1A receptors (K-d=0.34+/-0.12 nM and B-max=145+/-35 fmol/mg protein in rat hippocampal membrane homogenates). The binding is not sensitive to 100 mu M Gpp(NH)p. Initial autoradiography studies of rat brain sections exhibit regional localization consistent with the known 5-HT1A receptor distribution. This potential 5-HT1A antagonist ligand may provide a powerful tool for 5-HT1A receptor pharmacology studies in the central nervous system. (C) 1996 Wiley-Liss, Inc.