Synthesis and characterization of [125I]3′-(−)-iodopentazocine, a selective σ1 receptor ligand

George C. Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
European Journal of Pharmacology (Impact Factor: 2.53). 04/1997; 321(3):361-8. DOI: 10.1016/S0014-2999(96)00963-6
Source: PubMed


Pentazocine is a potent ligand at both opioid and sigma receptors, but with opposite stereoselectivities. Whereas (-)-pentazocine has high affinity for a number of opioid receptors, (+)-pentazocine labels sigma 1 receptors. Iodination of (-)-pentazocine at the 3'-position reverses its selectivity for opioid and sigma 1 receptors. 3'-(-)-Iodopentazocine competes at sigma 1 receptor binding sites with a Ki value of 8 nM, compared to approximately 40 nM for (-)-pentazocine. 3'-(-)-Iodopentazocine also has lost its affinity for opioid receptors. In contrast, iodination of (+)-pentazocine lowers its affinity at sigma 1 receptors. Synthesis of [125I]3'-(-)-iodopentazocine is readily performed with incorporations of up to 80%. Binding is of high affinity and shows the selectivity anticipated for a sigma 1 receptor-selective ligand. Exposing membranes prebound with [125I]3'-(-)-iodopentazocine to ultraviolet light can covalently couple the ligand into the membranes. Polyacrylamide gel electrophoresis reveals a major band at about 25 kDa and a minor one at about 20 kDa, indicating photolabeling of sigma 1 receptors with minor incorporation into sigma 2 sites.

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    • "Although (Ϫ)pentazocine labels ␮ and ␬ opioid binding sites with high affinity, it has only modest affinity for ␴ sites. Conversely, (ϩ)pentazocine selectivity labels ␴ 1 receptors (K i ϭ 1.8 nM) approximately 500-fold more potently than ␮ opioid sites (K i Ͼ 700 nM) and more than 30-fold more potently than ␬ 1 binding sites (Chien et al., 1997). Likewise, the ␴ ligand BD1047 shows poor affinity for opioid binding sites (K i Ͼ 1000 nM) while labeling ␴ 1 sites with very high affinity (K i ϭ 0.9 nM) (Matsumoto et al., 1995). "
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