Ziauddeen, H., Nathan, P., Dodds, C., Maltby, K., Miller, S.R., Waterworth, D., Song, K., Warren, L., Hosking, L., Zucchetto, M., Bush, M., Johnson, L.V., Sarai, B., Mogg, K., Bradley, B.P., Richards, D.B., Fletcher, P.C. and Bullmore, E.T. (2013) The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu-opioid receptor antagonist GSK1521498 in healthy subjects. The Journal of Clinical Pharmacology, 53 (10), 1078-1090.
Abstract
The mu-opioid system has a key role in hedonic and motivational processes critical to substance addiction. However, existing mu-opioid antagonists have had limited success as anti-addiction treatments. GSK1521498 is a selective and potent mu-opioid antagonist being developed for the treatment of overeating and substance addictions. In this study 28 healthy participants were administered single doses of GSK1521498 20mg, ethanol 0.5g/kg body weight, or both in combination, in a double blind placebo controlled four-way crossover design. The primary objective was to determine the risk of significant adverse pharmacodynamic (PD) and pharmacokinetic (PK) interactions. The effects of GSK1521498 on hedonic and consummatory responses to alcohol and the attentional processing of alcohol related stimuli, and their modulation by the OPRM1 A118G polymorphism were also explored. GSK1521498 20mg was well tolerated alone and in combination with ethanol. There were mild transient effects of GSK1521498 on alertness and mood that were greater when it was combined with ethanol. These effects were not of clinical significance. There were no effects of GSK1521498 on reaction time, hedonic or consummatory responses, nor were there interactions with genotype. These findings provide encouraging safety and pharmacokinetic data to support continued development of GSK1521498 for the treatment of alcohol addiction.
This record has no associated files available for download.
More information
Identifiers
Catalogue record
Export record
Contributors
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.