In vitro characterization of radioiodinated (+)-2-[4-(4-iodophenyl) piperidino]cyclohexanol [(+)-pIV] as a sigma-1 receptor ligand Original Research Article

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 (σ-1, σ-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 (σ-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 σ-1 receptor (Ki = 1.30 nM), was about 16 times higher than the sigma-2 (σ-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 Kd of 6.96 nM with a Bmax of 799 fmol/mg of protein. These results showed that (+)-pIV binds to the σ-1 receptor with greater affinity than sigma receptor ligands such as (+)-pentazocine or haloperidol, and that radioiodinated (+)-pIV is suitable as radiotracer for σ-1 receptor studies in vitro.