Synthesis and characterization of [125I]3'-(-)-iodopentazocine, a selective sigma 1 receptor ligand.
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.
Chien
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George C. Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Carroll
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Brown
G P
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Pan
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YX
Bowen
W
W
Pasternak
G W
GW
D000345:Affinity Labels; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007457:Iodine Radioisotopes; D008024:Ligands; D008099:Liver / Q000378:metabolism; D010423:Pentazocine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*
C106044:3'-iodopentazocine; D000345:Affinity Labels; D007457:Iodine Radioisotopes; D008024:Ligands; D017480:Receptors, sigma; D010423:Pentazocine