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Keywords:

  • Dextromethorphan;
  • paroxetine;
  • antitussives;
  • autoradiography;
  • 5-HT uptake;
  • σ receptors
  • The distribution and some pharmacological properties of centrally located dextromethorphan high-affinity binding sites were investigated by in vitro autoradiography.

  • Sodium chloride (50 mm) induced a 7 to 12 fold increase in dextromethorphan binding to rat brain in all areas tested. The effect of sodium was concentration-dependent with a higher dose (120 mm) exerting a smaller effect on binding.

  • [3H]-dextromethorphan binding in the presence of sodium was inhibited in the presence of the anticonvulsant phenytoin at a concentration of 100 μm, while the σ ligand (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)pipendine ((+)-PPP) had no effect on the binding, suggesting an interaction with the DM2 site.

  • The distribution of the sodium-dependent binding identified in this study correlated significantly with the distribution of the selective 5-HT uptake inhibitor [3H]-paroxetine, and paroxetine and dextromethorphan mutually displaced their binding at concentrations in the low nanomolar range.

  • These data show that dextromethorphan and paroxetine share a sodium-dependent high affinity binding site in rat brain, and suggest that dextromethorphan might interact, in the presence of sodium, with the 5-HT uptake mechanism in rat brain.

British Journal of Pharmacology (1997) 120, 1255–1262; doi:10.1038/sj.bjp.0701043