The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET.
BACKGROUND
Alterations in 5-HT2A receptor binding are implicated in suicidality and depression. 5-HT2A receptors may also be involved in the therapeutic effects of antidepressants.


OBJECTIVE
The purpose of this study was to assess the effect of paroxetine and nefazodone on 5-HT2A receptors after a single dose.


METHODS
Seven subjects received a single dose of nefazodone 200 mg and five subjects received a single dose of paroxetine 20 mg. Before and after the dose, 5-HT2A binding potentials (Bmax/Kd) were determined in each subject using [18F]-setoperone PET.


RESULTS
Nefazodone induced a significant change in 5-HT2A binding potential (-39+/-17%,, P = 0.003) while paroxetine showed no significant alteration of 5-HT2A binding potential (+3+/-13%, P = 0.73).


CONCLUSIONS
The change in 5-HT2A binding potential seen with nefazodone represents blockade of 5-HT2A receptors by the drug. We do not find evidence for acute downregulation of 5-HT2A receptors with paroxetine within 9 h.
Meyer
J H
JH
The Mood and Anxiety Division and PET Centre, The Clarke Division of the Centre for Addictions and Mental Health, Toronto, Ontario, Canada.
Cho
R
R
Kennedy
S
S
Kapur
S
S
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D010879:Piperazines; D011744:Pyrimidinones; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014230:Triazoles / Q000494:pharmacology*
D000928:Antidepressive Agents; D005462:Fluorine Radioisotopes; D010879:Piperazines; D011744:Pyrimidinones; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D014230:Triazoles; D017374:Paroxetine; C051752:nefazodone; C045359:setoperone