We compared the binding profiles of medications potentially useful in the treatment of involuntary emotional expression disorder at twenty-six binding sites in rat brain tissue membranes. Sites were chosen based on likelihood of being target sites for the mechanism of action of the agents in treating the disorder or their likelihood in producing side effects experienced by patients treated with psychoactive agents.We used radioligand binding assays employing the most selective labeled ligands available for sites of interest. Concentrations of labeled ligand were used at or below the K i value of the ligand for the target site. Compounds were initially screened at 1 μM. For compounds that competed for greater than 20–30% of specific binding at target sites of interest, full concentration curves were constructed. Dextromethorphan, amitriptyline and fluoxetine competed for binding to σ 1 receptors and to serotonin transporters with high to moderate affinity. Of the target sites tested, these are the most likely to contribute to the therapeutic benefit of the various agents. In addition, all three drugs showed some activity at α 2 and 5-HT 1B/D sites. Of the drugs tested, dextromethorphan bound to the fewest sites unlikely to be target sites. Although the mechanism of action of dextromethorphan or any drug that has been used in the treatment of involuntary emotional expression disorder is currently unknown, our data support that the affinity of the drug for σ 1 receptors is consistent with its possible action through this receptor type in controlling symptoms of the disorder.