Altered [3H]imipramine and 5-HT2 but not [3H]paroxetine binding sites in platelets from depressed patients.
BACKGROUND
Serotonergic system alterations were studied in 51 depressed patients classified according to DSM-III-R criteria for major depression with melancholia compared to 31 healthy controls.


METHODS
[3H]Imipramine and [3H]paroxetine binding sites and the 5HT2 receptor were simultaneously determined in blood platelet membranes.


RESULTS
A significantly lower maximum binding in [3H]imipramine binding was observed in depressed patients compared to controls (1134+/-74 vs. 1712+/-106 fmol/mg protein, P<0.0001) without changes in the equilibrium dissociation constant (1.10+0.05 vs. 1.25-/+0.09 nM). [3H]Paroxetine binding did not differ between the two groups (Bmax, 1441+/-55 vs. 1280+/-81 fmol/mg protein; Kd, 0.060+/-0.002 vs. 0.062+/-0.002 nM). The K(d) value of 5HT2 binding was lower in depressed patients than controls (0.95+/-0.04 vs. 1.15+/-0.09 nM, P<0.039) without changes in maximum binding (140+/-11 vs. 127+/-14 fmol/mg protein).


CONCLUSIONS
Taken together, these results suggest that [3H]imipramine and 5HT2 receptors may be good biological markers for serotonergic dysfunction in depressive disorders.
Rosel
P
P
Department of Biochemistry, Hospitalet de Llobregat, Barcelona, Spain.
Arranz
B
B
Vallejo
J
J
Alvarez
P
P
Menchon
J M
JM
Palencia
T
T
Navarro
M A
MA
D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects*; D015415:Biomarkers; D002462:Cell Membrane / Q000378:metabolism; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000523:psychology; D005260:Female; D006801:Humans; D007099:Imipramine / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood* / Q000494:pharmacology* / Q000627:therapeutic use; D011985:Receptors, Serotonin / Q000097:blood* / Q000378:metabolism*
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D015415:Biomarkers; D011985:Receptors, Serotonin; D017374:Paroxetine; D007099:Imipramine