Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.

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...

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मुख्य लेखकों: Harmer, C, Dawson, G, Dourish, C, Favaron, E, Parsons, E, Fiore, M, Zucchetto, M, Bifone, A, Poggesi, I, Fernandes, S, Alexander, R, Goodwin, G
स्वरूप: Journal article
भाषा:English
प्रकाशित: 2013
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author Harmer, C
Dawson, G
Dourish, C
Favaron, E
Parsons, E
Fiore, M
Zucchetto, M
Bifone, A
Poggesi, I
Fernandes, S
Alexander, R
Goodwin, G
author_facet Harmer, C
Dawson, G
Dourish, C
Favaron, E
Parsons, E
Fiore, M
Zucchetto, M
Bifone, A
Poggesi, I
Fernandes, S
Alexander, R
Goodwin, G
author_sort Harmer, C
collection OXFORD
description 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.
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spelling oxford-uuid:d81b14b0-53b1-47df-8f68-c6a9cfdfb1bf2022-03-27T08:45:56ZCombined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d81b14b0-53b1-47df-8f68-c6a9cfdfb1bfEnglishSymplectic Elements at Oxford2013Harmer, CDawson, GDourish, CFavaron, EParsons, EFiore, MZucchetto, MBifone, APoggesi, IFernandes, SAlexander, RGoodwin, G 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.
spellingShingle Harmer, C
Dawson, G
Dourish, C
Favaron, E
Parsons, E
Fiore, M
Zucchetto, M
Bifone, A
Poggesi, I
Fernandes, S
Alexander, R
Goodwin, G
Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
title Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
title_full Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
title_fullStr Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
title_full_unstemmed Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
title_short Combined NK₁ antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.
title_sort combined nk₁ antagonism and serotonin reuptake inhibition effects on emotional processing in humans
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