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The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu-opioid receptor antagonist GSK1521498 in healthy subjects.

The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu-opioid receptor antagonist GSK1521498 in healthy subjects.
The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu-opioid receptor antagonist GSK1521498 in healthy subjects.
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.
0091-2700
1078-1090
Ziauddeen, H.
0396c9e6-2cc5-4e31-9872-bc7f2342ec8f
Nathan, P.
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Dodds, C.
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Maltby, K.
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Miller, S.R.
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Waterworth, D.
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Song, K.
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Warren, L.
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Hosking, L.
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Zucchetto, M.
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Bush, M.
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Johnson, L.V.
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Sarai, B.
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Mogg, K.
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Bradley, B.P.
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Richards, D.B.
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Fletcher, P.C.
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Bullmore, E.T.
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Ziauddeen, H.
0396c9e6-2cc5-4e31-9872-bc7f2342ec8f
Nathan, P.
52aeacc6-c908-4819-b5c6-4ce2ed19032c
Dodds, C.
3f10f0af-bd22-4c57-9dfa-9faa31f3ba66
Maltby, K.
37e807f2-5bc0-4ec9-a343-ff173f3983d3
Miller, S.R.
18c85c76-d596-4bb9-b3ae-9979ba711157
Waterworth, D.
da881f02-310f-455c-b3ef-9b8aa9467457
Song, K.
8c11d970-f870-40f4-ab04-2edf6e688d2f
Warren, L.
91eda9be-8629-4b6b-b39d-ff85e5ac2ffc
Hosking, L.
a7a16392-3363-4caa-8696-a81a194032e2
Zucchetto, M.
11a1964a-7c3b-4254-9547-e242659b91ff
Bush, M.
5ff0ad85-ade2-4172-82ae-71639a64450d
Johnson, L.V.
89b9f54e-1b52-4e60-b376-cced2b772297
Sarai, B.
a03e5abe-c43e-49c7-8706-45ba24b0d963
Mogg, K.
5f1474af-85f5-4fd3-8eb6-0371be848e30
Bradley, B.P.
bdacaa6c-528b-4086-9448-27ebfe463514
Richards, D.B.
e9d017c3-eecc-449b-9969-e065ab01ead2
Fletcher, P.C.
219353d0-b519-4fc3-9b70-cac16bb0ee0c
Bullmore, E.T.
46e467e1-92f4-4bd4-a655-b3fe7b7d56d0

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.

Record type: Article

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.

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More information

Accepted/In Press date: 11 May 2013
Published date: 2013
Organisations: Clinical Neuroscience

Identifiers

Local EPrints ID: 352452
URI: https://eprints.soton.ac.uk/id/eprint/352452
ISSN: 0091-2700
PURE UUID: 017775e3-b1f7-4216-b25c-2462206977b7
ORCID for B.P. Bradley: ORCID iD orcid.org/0000-0003-2801-4271

Catalogue record

Date deposited: 14 May 2013 11:07
Last modified: 20 Jul 2019 01:06

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Contributors

Author: H. Ziauddeen
Author: P. Nathan
Author: C. Dodds
Author: K. Maltby
Author: S.R. Miller
Author: D. Waterworth
Author: K. Song
Author: L. Warren
Author: L. Hosking
Author: M. Zucchetto
Author: M. Bush
Author: L.V. Johnson
Author: B. Sarai
Author: K. Mogg
Author: B.P. Bradley ORCID iD
Author: D.B. Richards
Author: P.C. Fletcher
Author: E.T. Bullmore

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