125I-Bolton-Hunter-8-methoxy-2-[N-propyl-N-propylamino]tetralin as a new selective radioligand of 5-HT1A sites in the rat brain. In vitro binding and autoradiographic studies.

In vitro binding assays with 125I-[8-methoxy-2-[N-propyl-N-(3'-iodo-4'-hydroxyphenyl)-propionamido -N'- propylamino] tetralin] (125I-BH-8-MeO-N-PAT), a 125I-labeled derivative of the potent serotonin (5-HT) agonist 8-hydroxy-2-[di-n-propylamino]tetralin [( 3H]-8-OH-DPAT), showed that this compound recognized specific sites with nanomolar affinity for 5-HT and 5-HT1A ligands such as spiroxatrine, ipsapirone, buspirone and gepirone in rat hippocampal membranes. Comparison of the binding characteristics of 125I-BH-8-MeO-N-PAT with those of [3H]-8-OH-DPAT revealed striking similarities: at the hippocampal level, both binding sites exhibited nanomolar affinity for their respective ligands and the same Bmax; their pharmacological profiles defined by the inhibition of each bound ligand by a series of 26 serotonin, dopamine- or norepinephrine-related agonists and antagonists were identical; and their regional distributions examined by membrane binding assays and autoradiography of labeled brain sections were highly correlated. These observations indicate that 125I-BH-8-MeO-N-PAT is the first 125I-reversible ligand for the selective labeling of 5-HT1A sites in the rat central nervous system.