• Article

Synthesis and characterization of [I-125]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 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 sigma(1) receptors. Synthesis of [I-125]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 [I-125]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

Citation

Chien, C. C., Carroll, F., Brown, G. P., Pan, Y. X., Bowen, W., & Pasternak, G. W. (1997). Synthesis and characterization of [I-125]3'-(-)-iodopentazocine, a selective sigma(1) receptor ligand. European Journal of Pharmacology, 321(3), 361-368.