Synthesis and characterization of [125I]3′-(−)-iodopentazocine, a selective σ1 receptor ligand
| Autor: | Chih Cheng Chien, Gavril W. Pasternak, Ying-Xian Pan, George P. Brown, Wayne D. Bowen, Carroll Fi |
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| Rok vydání: | 1997 |
| Předmět: |
Pharmacology
Pentazocine Sigma-1 receptor biology Stereochemistry Ligand Affinity label Cell Membrane fungi Sigma receptor Affinity Labels Ligands Cell Line Rats Benzomorphan Iodine Radioisotopes chemistry.chemical_compound Liver chemistry Ultraviolet light biology.protein Animals Receptors sigma Binding site Receptor |
| Zdroj: | European Journal of Pharmacology. 321:361-368 |
| ISSN: | 0014-2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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