title: Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
abstract: BACKGROUND
  Synergistic effects of NK₁ receptor antagonism combined with serotonin reuptake inhibition have been reported in preclinical models. GSK424887 is a selective competitive antagonist of the human NK₁ receptor and inhibitor of the serotonin transporter. However, its actions in human models of depression have not been assessed.
  
  
  METHODS
  This study explored the effects of acute administration of GSK424887 compared to placebo in healthy male volunteers. The selective serotonin reuptake inhibitor (SSRI) citalopram was used as a positive control. A battery of emotional processing tasks was given at the peak time of drug effect.
  
  
  RESULTS
  GSK424887 enhanced attentional vigilance in the dot-probe task to both positive and negative stimuli. By contrast, citalopram enhanced perception of angry, sad and happy facial expressions and increased positive bias in the facial expression recognition task. Neither drug significantly affected emotion potentiated startle responses or emotional memory.
  
  
  CONCLUSIONS
  These results suggest that acute administration of GSK424887 modulated some aspects of emotional processing but these effects were not similar to those seen previously with antidepressant agents. This was the first use of the battery of emotional processing tasks in a Phase 1 study. Repeated administration of the test and active control drugs may be needed to reliably characterise their effects.
authors: Department of Psychiatry, University of Oxford, Oxford, UK. Catherine.harmer@psych.ox.ac.uk
authors: Catherine J
authors: CJ
authors: Harmer
authors: Gerry R
authors: GR
authors: Dawson
authors: Colin T
authors: CT
authors: Dourish
authors: Elisa
authors: E
authors: Favaron
authors: Elizabeth
authors: E
authors: Parsons
authors: Monica
authors: M
authors: Fiore
authors: Mauro
authors: M
authors: Zucchetto
authors: Angelo
authors: A
authors: Bifone
authors: Italo
authors: I
authors: Poggesi
authors: Sofia
authors: S
authors: Fernandes
authors: Robert C
authors: RC
authors: Alexander
authors: Guy M
authors: GM
authors: Goodwin
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D005149:Facial Expression; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010465:Perception / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use*; D021641:Recognition, Psychology / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D015283:Citalopram; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; C584556:N-(1-(3-chloro-1-naphthalenyl)ethyl)-2-(4-(4-fluorophenyl)-1-methyl-4-piperidinyl)-N-methylacetamide