This will be a phase I, single centre, randomised, double blind, double-dummy, placebo controlled, parallel group single-dose study in healthy volunteers. The purpose of this study is to assess the effect of a single-dose administration of GSK424887, a potent, selective competitive antagonist of the human Neurokinin 1 (NK1) receptor and a potent inhibitor of the human serotonin transporter (SERT), at the maximum dosage of 100 mg versus placebo and versus citalopram (20 mg) on emotional processing in healthy male volunteers. Pharmacokinetics and safety following oral administration of GSK424887 will be also evaluated. An Emotional Test Battery (ETB) previously used to characterise the effects of antidepressants on positive and negative emotion processing in Healthy Volunteers and patients will be used. We hypothesise that GSK424887 will modulate emotional information processing acutely. We anticipate that these effects may be manifest at sub-effective levels of NK1 and SERT receptor occupancy, thus providing pharmacodynamic evidence of the synergistic interaction of the two mechanisms in humans.

Inclusion Criteria:

1. Healthy males with no neurological, or history of psychiatric illness
2. Aged between 18 and 45 years
3. Agree to use contraception
4. BMI range of 18 to 33 kg/m²
5. Fluent English speakers
6. Non smoker or light smoker

Exclusion Criteria:

1. Positive pre-study drug/alcohol screen or regular alcohol consumption
2. Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
3. On prescription or non prescription drug
4. Exposure to more than four new chemical entities within 12 months prior to the first dosing day
5. Consumption of large amounts of caffeinated drinks
6. Significant hearing impairment
7. Previous experience of the emotional test battery experimental procedures

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.