Synthesis and characterization of [(125)I]3'-(-)-iodopentazocine, a selective σ(1) receptor ligand Journal Article
| Authors: | Chien, C. C.; Carroll, F. I.; Brown, G. P.; Pan, Y. X.; Bowen, W.; Pasternak, G. W. |
| Article Title: | Synthesis and characterization of [(125)I]3'-(-)-iodopentazocine, a selective σ(1) receptor ligand |
| Abstract: | Pentazocine is a potent ligand at both opioid and a receptors, but with opposite stereoselectivities. Whereas (-)-pentazocine has high affinity for a number of opioid receptors, (+)-pentazocine labels σ1 receptors. Iodination of(-)-pentazocine at the 3'-position reverses its selectivity for opioid and σ1 receptors. 3'-(-)-Iodopentazocine competes at σ1 receptor binding sites with a K(i) 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 σ1 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 σ1 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 a, receptors with minor incorporation into σ2 sites. |
| Keywords: | controlled study; nonhuman; comparative study; ultraviolet radiation; animal cell; animal; metabolism; animals; opiate; cell line; drug synthesis; drug receptor binding; liver; chemistry; iodine 125; radioactive iodine; isotope labeling; iodine radioisotopes; neuroblastoma cell; rat; cell membrane; ligand; drug derivative; ligands; rats; stereochemistry; membrane binding; polyacrylamide gel electrophoresis; enkephalin[2,5 dextro penicillamine]; photoaffinity labeling; affinity labeling; receptor subtype; pentazocine; receptors, sigma; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; enantiomer; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; affinity label; affinity labels; priority journal; article; sigma opiate receptor; enkephalin[2 dextro alanine 5 dextro leucine]; σ receptor; benzomorphane; 1,3 bis(2 methylphenyl)guanidine; 3' iodopentazocine; 3'-iodopentazocine; liver membrane |
| Journal Title: | European Journal of Pharmacology |
| Volume: | 321 |
| Issue: | 3 |
| ISSN: | 0014-2999 |
| Publisher: | Elsevier B.V. |
| Date Published: | 1997-03-05 |
| Start Page: | 361 |
| End Page: | 368 |
| Language: | English |
| DOI: | 10.1016/s0014-2999(96)00963-6 |
| PUBMED: | 9085049 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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