Acute effects of venlafaxine and paroxetine on serotonergic transmission in human volunteers.
BACKGROUND
Antidepressant drugs are thought to enhance serotonergic neurotransmission through postsynaptic 5-HT(1A) receptors. This effect is delayed in animals and may be paralleled by a delay in the onset of a clinical response in humans. In humans, the growth hormone (GH) response to intravenous l-tryptophan (IV l-TRP) is blocked by the 5-HT(1A) antagonist pindolol and the prolactin response is blunted. Both are therefore thought to be a useful measure of 5-HT(1A) receptor function. Clomipramine has previously been found to enhance the GH and prolactin responses to IV l-TRP after only 2 h.


OBJECTIVE
The purpose of this study was to use this method to investigate the effects of newer antidepressants on 5-HT(1A) receptor-mediated function.


METHODS
Twelve healthy male volunteers took part in a random order, double blind study, in which 18.75 mg venlafaxine, 5 mg paroxetine or placebo was administered 3 h before infusion of l-TRP.


RESULTS
Pretreatment with venlafaxine significantly enhanced the growth hormone (GH) response to the infusion compared with pretreatment with placebo. There was no significant difference between the GH response following paroxetine compared with placebo or with venlafaxine.


CONCLUSIONS
The data suggest enhancement of transmission through postsynaptic 5-HT(1A) receptors by venlafaxine but not paroxetine, after only 3 h.
Porter
R J
RJ
Department of Neuroscience and Psychiatry, University of Newcastle, Royal Victoria Infirmary, Newcastle NE1 4LP, UK.
McAllister-Williams
R H
RH
Young
A H
AH
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002997:Clomipramine / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D017374:Paroxetine / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014364:Tryptophan / Q000097:blood / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride; D014839:Vomiting / Q000139:chemically induced
D002997:Clomipramine; D003511:Cyclohexanols; D019382:Human Growth Hormone; D017374:Paroxetine; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; D000069470:Venlafaxine Hydrochloride