Pharmacokinetics and central nervous system effects of the novel dual NK1/NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers



Dr E.T. te Beek MD, Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, the Netherlands.

Tel.: +31 (0)71 524 6400

Fax: +31 (0)71 524 6499




Antagonism of both NK1 and NK3 receptors may be an effective strategy in the pharmacotherapy of schizophrenia, drug addiction or depression. GSK1144814 is a novel selective dual NK1/NK3 receptor antagonist. The potential influence of GSK1144814 on the effects of alcohol was investigated.


In a blinded, randomized, placebo-controlled, two period crossover study, the pharmacokinetics and central nervous system (CNS) effects of single oral doses of 200 mg GSK1144814 were evaluated in 20 healthy volunteers, using a controlled alcohol infusion paradigm to maintain stable alcohol concentrations with subsequent analysis of eye movements, adaptive tracking, body sway, visual analogue scales, Epworth sleepiness scale and the verbal visual learning test.


Frequent adverse effects were mild somnolence, fatigue and headache. Plasma concentration of GSK1144814 in the presence of alcohol was maximal 1.5 h after dose administration. GSK1144814 did not affect alcohol pharmacokinetics. Co-administration of GSK1144814 and alcohol impaired saccadic reaction time and peak velocity, adaptive tracking, alertness, sleepiness, word recognition and recognition reaction time compared with administration of alcohol alone, but the size of the interaction was small.


Administration of GSK1144814 in the presence of alcohol was generally well tolerated and not likely to produce clinically relevant additional impairments after alcohol consumption.