AN AUTORADIOGRAPHIC STUDY OF DEXTROMETHORPHAN HIGH-AFFINITY BINDING-SITES IN RAT-BRAIN - SODIUM-DEPENDENCY AND COLOCALIZATION WITH PAROXETINE

1 The distribution and some pharmacological properties of centrally lo cated dextromethorphan high-affinity binding sites were investigated b y in vitro autoradiography. 2 Sodium chloride (50 mM) induced a 7 to 1 2 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.3 [H-3]-dextrometh orphan binding in the presence of sodium was inhibited in the presence of the anticonvulsant phenytoin at a concentration of 100 mu M, while the sigma ligand (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)pipendine ((+)- PPP) had no effect on the binding, suggesting an interaction with the DM(2) site. 4 The distribution of the sodium-dependent binding identif ied in this study correlated significantly with the distribution of th e selective 5-HT uptake inhibitor [H-3]-paroxetine, and paroxetine and dextromethorphan mutually displaced their binding at concentrations i n the low nanomolar range. 5 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 prese nce of sodium, with the 5-HT uptake mechanism in rat brain.