[3H]paroxetine binding in rat frontal cortex strongly correlates with [3H]5-HT uptake: effect of administration of various antidepressant treatments.
Paroxetine is a selective and potent inhibitor of 5-hydroxytryptamine (5-HT) uptake into serotonergic neurones. [3H]Paroxetine binding to rat frontal cortex was of high affinity with a high percentage of specific binding. The binding data of both competition and saturation studies fitted a single site binding model. [3H]Paroxetine binding was potently inhibited by the selective 5-HT uptake inhibitors. In addition, a very good correlation was demonstrated between the ability of twenty-three compounds to inhibit [3H]paroxetine binding to rat frontal cortical membranes and [3H]5-HT uptake into rat frontal cortical synaptosomes. These data support the view that [3H]paroxetine binds to a single site which corresponds to the 5-HT uptake site. Using this ligand, the effects of repeated administration of antidepressant drugs with a wide range of pharmacological actions and electroconvulsive shock on 5-HT reuptake sites were examined. [3H]Paroxetine binding parameters (Kd and Bmax) were unaltered by all treatments. It would, therefore, appear that antidepressant therapy does not produce adaptive changes in 5-HT uptake sites.
Cheetham
S C
SC
Boots Pharmaceuticals Research Department, Nottingham, U.K.
Viggers
J A
JA
Slater
N A
NA
Heal
D J
DJ
Buckett
W R
WR
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004597:Electroshock; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017374:Paroxetine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D017374:Paroxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors