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An autoradiographic study of dextromethorphan high‐affinity binding sites in rat brain: sodium‐dependency and colocalization with paroxetine
Author(s) -
Meoni P.,
Tortella F. C.,
Bowery N. G.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701043
Subject(s) - dextromethorphan , chemistry , sodium , binding site , paroxetine , dextrorphan , pharmacology , distribution (mathematics) , biochemistry , receptor , serotonin , biology , mathematical analysis , mathematics , organic chemistry
The distribution and some pharmacological properties of centrally located dextromethorphan high‐affinity binding sites were investigated by in vitro autoradiography. Sodium chloride (50 m m ) 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 m m ) exerting a smaller effect on binding. [ 3 H]‐dextromethorphan binding in the presence of sodium was inhibited in the presence of the anticonvulsant phenytoin at a concentration of 100 μ m , while the σ ligand (+)‐3‐(‐3‐hydroxyphenyl)‐N‐(1‐propyl)pipendine ((+)‐PPP) had no effect on the binding, suggesting an interaction with the DM 2 site. The distribution of the sodium‐dependent binding identified in this study correlated significantly with the distribution of the selective 5‐HT uptake inhibitor [ 3 H]‐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