title: In vitro characterization of radioiodinated (+)-2-[4-(4-iodophenyl) piperidino]cyclohexanol [(+)-pIV] as a sigma-1 receptor ligand.
abstract: We investigated the binding characteristics of a (+)-enantiomer of radioiodinated 2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[125I]pIV], radioiodinated at the para-position of the 4-phenylpiperidine moiety, to sigma receptors (sigma-1, sigma-2) and to vesicular acetylcholine transporters (VAChT) in membranes of the rat brain and liver. In competitive inhibition studies, (+)-pIV (Ki=1.30 nM) had more than 10 times higher affinity to the sigma-1 (sigma-1) receptor than (+)-pentazocine (Ki=19.9 nM) or haloperidol (Ki=13.5 nM) known as sigma ligands. Also, the binding affinity of (+)-pIV for the sigma-1 receptor (Ki=1.30 nM), was about 16 times higher than the sigma-2 (sigma-2) receptor (Ki=20.4 nM). (+)-pIV (Ki=1260 nM) had a much lower affinity for VAChT than (-)-vesamicol (Ki=13.0 nM) or (-)-pIV (Ki=412 nM). (+)-[125I]pIV had low affinity for the dopamine, serotonin, adrenaline, and acetylcholine receptors. Furthermore, in a saturation binding study, (+)-[125I]pIV exhibited a K) of 6.96 nM with a Bmax of 799 fmol/mg of protein. These results showed that (+)-pIV binds to the sigma-1 receptor with greater affinity than sigma receptor ligands such as (+)-pentazocine or haloperidol, and that radioiodinated (+)-pIV is suitable as radiotracer for sigma-1 receptor studies in vitro.
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8640, Japan. shiba@med.kanazawa-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000818:Animals; D003511:Cyclohexanols / Q000737:chemistry / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D003511:Cyclohexanols; D007457:Iodine Radioisotopes; D008024:Ligands; D010880:Piperidines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C502476:2-(4-(4-iodophenyl) piperidino)cyclohexanol