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.
Gozlan
H
H
Institut National de la Santé et de La Recherche Médicale U. 288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Ponchant
M
M
Daval
G
G
Verge
D
D
Menard
F
F
Vanhove
A
A
Beaucourt
J P
JP
Hamon
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008024:Ligands; D008297:Male; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
D007457:Iodine Radioisotopes; D008024:Ligands; D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C055126:8-methoxy-2-(N-propyl-N-(3'-iodo-4'-hydroxyphenyl)-propionamido-N'-propylamino)tetralin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin