An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine
Article first published online: 17 FEB 2009
1997 British Pharmacological Society
British Journal of Pharmacology
Volume 120, Issue 7, pages 1255–1262, March 1997
How to Cite
Meoni, P., Tortella, F. C. and Bowery, N. G. (1997), An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine. British Journal of Pharmacology, 120: 1255–1262. doi: 10.1038/sj.bjp.0701043
- Issue published online: 17 FEB 2009
- Article first published online: 17 FEB 2009
- (Received September 23, 1996, Revised December 11, 1996, Accepted January 3, 1997)
- 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