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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Administration of GSK1144814 in the presence of alcohol was generally well tolerated and not likely to produce clinically relevant additional impairments after alcohol consumption.
Centre for Human Drug Research, Leiden, The Netherlands. etbeek@chdr.nl
Erik T
ET
te Beek
Justin L
JL
Hay
Jonathan N
JN
Bullman
Clare
C
Burgess
Kimberly J
KJ
Nahon
Erica S
ES
Klaassen
Frank A
FA
Gray
Joop M A
JM
van Gerven
D000293:Adolescent; D000328:Adult; D000368:Aged; D000435:Alcoholic Intoxication / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064729:Neurokinin-1 Receptor Antagonists; D011597:Psychomotor Performance / Q000187:drug effects*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism; D055815:Young Adult
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D000431:Ethanol