Different brain kinetics of two sigma 1 receptor ligands, [3H](+)-pentazocine and [11C]SA4503, by P-glycoprotein modulation

Synapse. 2003 May;48(2):80-6. doi: 10.1002/syn.10190.


We compared the brain kinetics of radiolabeled (+)-pentazocine and SA4503, which have a high and selective affinity for sigma(1) receptors. Brain uptake of [(11)C]SA4503 was high after intravenous injection followed by a gradual decrease in mice, whereas that of [(3)H](+)-pentazocine rapidly decreased. The brain uptake of the two radioligands was dose-dependently reduced, but the reduction of [(3)H](+)-pentazocine was found at higher doses. Percentages of the saturable binding of [(3)H](+)-pentazocine was much lower than that of [(11)C]SA4503. The brain uptake of [(3)H](+)-pentazocine was greatly blocked by SA4503 at a dose of 2 micromol/kg, while that of [(11)C]SA4503 was blocked by (+)-pentazocine at a dose of 20 micromol/kg and over. When mice were treated with cyclosporin A, a P-glycoprotein modulator, the uptake of [(3)H](+)-pentazocine was enhanced, but that of [(11)C]SA4503 was not. Under control and P-glycoprotein-modulated conditions, the brain uptake of both radioligands was reduced by haloperidol, another representative sigma receptor ligand, to a different extent. We concluded that the P-glycoprotein modulation resulted in the different brain kinetics of the two radioligands. The radiolabeled SA4503 is suitable as an in vivo probe, but radiolabeled (+)-pentazocine is not.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Brain / metabolism*
  • Carbon Radioisotopes / metabolism
  • Mice
  • Pentazocine / chemistry
  • Pentazocine / metabolism*
  • Pharmacokinetics
  • Piperazines / chemistry
  • Piperazines / metabolism*
  • Radioligand Assay / methods*
  • Receptors, sigma / metabolism*
  • Tritium / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carbon Radioisotopes
  • Piperazines
  • Receptors, sigma
  • sigma-1 receptor
  • Tritium
  • SA 4503
  • Pentazocine