Pharmacokinetics and central nervous system effects of the novel dopamine D3
receptor antagonist GSK598809 and intravenous alcohol infusion at pseudo-steady
state.
Author(s): te Beek ET, Zoethout RW, Bani MS, Andorn A, Iavarone L, Klaassen ES, Fina P, van
Gerven JM.
Affiliation(s): Centre for Human Drug Research, Leiden, the Netherlands. etbeek@chdr.nl
Publication date & source: 2012, J Psychopharmacol. , 26(2):303-14
GSK598809 is a novel selective dopamine D(3) receptor antagonist, currently in
development for the treatment of substance abuse and addiction. In a blinded,
randomized, placebo-controlled study, effects of single oral doses of 175 mg
GSK598809 were evaluated in healthy volunteers. Pharmacokinetics, central nervous
system (CNS) effects and potential for interactions with alcohol were evaluated,
using an alcohol infusion paradigm and analysis of eye movements, adaptive
tracking, visual analogue scales, body sway, serum prolactin and verbal visual
learning test. Adverse effects of GSK598809 included headache, dizziness and
somnolence. Plasma concentration of GSK598809 was maximal 2-3 hours postdose and
decreased with a half-life of roughly 20 hours. CNS effects were limited to
prolactin elevation and decreased adaptive tracking. Co-administration of
GSK598809 and alcohol did not affect alcohol pharmacokinetics, but caused a 9%
decrease of C (max) and a 15% increase of AUC of GSK598809. CNS effects of
co-administration were mainly additive, except a small supra-additive increase in
saccadic reaction time and decrease in delayed word recall. In conclusion,
GSK598809 causes elevation of serum prolactin and a small decrease in adaptive
tracking performance. After co-administration with alcohol, effects of GSK598809
are mainly additive and the combination is well tolerated in healthy volunteers.
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