Pharmacological characterization of the serotonin transporter in young and elderly subjects.
The potency of some tricyclics (imipramine and clomipramine) and selective 5-HT reuptake inhibitors (fluoxetine, paroxetine, and citalopram) in displacing the [(3)H]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.
Marazziti
D
D
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Italy. dmarazzi@psico.med.unipi.it
Baroni
S
S
Rossi
A
A
Masala
I
I
Giannaccini
G
G
Gori
V
V
Lucacchini
A
A
Cassano
G B
GB
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000187:drug effects*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human