An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine

摘要

class="enumerated" style="list-style-type:decimal">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.