Pharmacological Characterization of the Serotonin Transporter in Young and Elderly Subjects

Abstract

The potency of some tricyclics (imipramine and clomipramine) and selective 5-HT reuptake inhibitors (fluoxetine, paroxetine, and citalopram) in displacing the [³H]paroxetine binding to platelet membranes was measured in young and elderly subjects of both sexes. The results showed that the most potent compound in all subjects was paroxetine, followed by clomipramine, citalopram, fluoxetine, and imipramine, with no differences between male and female subjects. All drugs, except paroxetine and clomipramine, showed significantly lower pKi values in the elderly subjects of both sexes. These findings would suggest that although the pharmacological profile of the 5-HT transporter is not modified qualitatively by age, quantitative changes in its affinity do perhaps occur which would justify more careful studies on this topic in order to get optimal dosages of drugs acting at this level.

Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a review

“…Paroxetine's inhibition of NE uptake may contribute to its better efficacy at higher doses . The pharmacological profile of the 5-HT transporter is not modified qualitatively by age, but quantitative changes in its affinity occur with paroxetine, pK i values decrease in elderly subjects of both sexes (Marazziti et al, 2001). In elderly patients, plasma concentrations of paroxetine at steady state are higher and the terminal elimination half-life is longer than those reported in younger subjects (Budman et al, 1995).…”