Imperial College London
Alternate

Dr Sue Wilson

Faculty of Medicine, Department of Brain Sciences

Honorary Senior Research Fellow
 
 
 
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Contact

 

sue.wilson

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lingford-Hughes:2018:10.3389/fpsyt.2018.00664,
author = {Lingford-Hughes, A and Durant, C and Paterson, L and Turton, S and Venkataraman, A and Wilson, S and Myers, J and Muthukumaraswamy, S and Mick, I and Paterson, S and Jones, T and Nahar, L and Cordero, R and Nutt, D},
doi = {10.3389/fpsyt.2018.00664},
journal = {Frontiers in Psychiatry},
title = {Using baclofen to explore GABA-B receptor function in alcohol dependence: insights from pharmacokinetic and pharmacodynamic measures},
url = {http://dx.doi.org/10.3389/fpsyt.2018.00664},
volume = {9},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: The role of GABA-B neurotransmission in addiction has recently received increased attention, with clinical trials indicating that baclofen, a GABA-B receptor agonist, may reduce alcohol consumption, craving and promote abstinence. However, the optimal dose to treat alcohol dependence is unclear with patients requesting and tolerating much higher doses of baclofen, compared with other clinical uses. We assessed the pharmacokinetics and pharmacodynamics (PK/PD) of baclofen to provide insight into GABA-B sensitivity in this patient group, relative to controls.Methods: Male healthy volunteers (controls, n = 12) and abstinent alcohol dependent individuals (AD, n = 8) received single oral doses of baclofen or placebo in a 3-way crossover design. Controls received placebo/10 mg/60 mg baclofen in a randomized, double-blind design, AD received placebo/60 mg/90 mg baclofen in a single-blind design. PK/PD measures were recorded at baseline and multiple time-points up to 6 h post-dosing, including plasma baclofen, plasma growth hormone (GH), Subjective High Assessment Scale (SHAS) and biphasic alcohol effects scale (BAES). Repeated measures ANOVA analysis explored “change from baseline” dose, time, group, and interaction effects, t-tests compared peak effects.Results: Dose-dependent effects of baclofen on PK and PD measures were observed in both control and AD groups. Whilst there were no significant group differences in any baclofen PK parameters (t1/2, tmax, Cmax, AUC), marked differences in PD effects were clearly evident. In controls, 60 mg baclofen significantly increased total SHAS and BAES scores, and significantly increased plasma GH levels compared with placebo, with peak effects at 60–120 min, in line with its PK profile. In AD, 60 mg baclofen had limited effects on these parameters; SHAS scores, BAES scores and plasma GH levels were significantly blunted compared with controls (significant grouptime interactions P = 0.0014, 0.0015 and P
AU  - Lingford-Hughes,A
AU  - Durant,C
AU  - Paterson,L
AU  - Turton,S
AU  - Venkataraman,A
AU  - Wilson,S
AU  - Myers,J
AU  - Muthukumaraswamy,S
AU  - Mick,I
AU  - Paterson,S
AU  - Jones,T
AU  - Nahar,L
AU  - Cordero,R
AU  - Nutt,D
DO  - 10.3389/fpsyt.2018.00664
PY  - 2018///
SN  - 1664-0640
TI  - Using baclofen to explore GABA-B receptor function in alcohol dependence: insights from pharmacokinetic and pharmacodynamic measures
T2  - Frontiers in Psychiatry
UR  - http://dx.doi.org/10.3389/fpsyt.2018.00664
UR  - http://hdl.handle.net/10044/1/66465
VL  - 9
ER  -
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