title: Differences between magnetoencephalographic (MEG) spectral profiles of drugs acting on GABA at synaptic and extrasynaptic sites: a study in healthy volunteers.
abstract: A range of medications target different aspects of the GABA system; understanding their effects is important to inform further drug development. Effects on the waking EEG comparing these mechanisms have not been reported; in this study we compare the effects on resting MEG spectra of the benzodiazepine receptor agonist zolpidem, the delta sub-unit selective agonist gaboxadol (also known as THIP) and the GABA reuptake inhibitor tiagabine. These were two randomised, single-blind, placebo-controlled, crossover studies in healthy volunteers, one using zolpidem 10 mg, gaboxadol 15 mg and placebo, and the other tiagabine 15 mg and placebo. Whole head MEG recordings and individual MEG spectra were divided into frequency bands. Baseline spectra were subtracted from each post-intervention spectra and then differences between intervention and placebo compared. After zolpidem there were significant increases in beta frequencies and reduction in alpha frequency power; after gaboxadol and tiagabine there were significant increases in power at all frequencies up to beta. Enhancement of tonic inhibition via extrasynaptic receptors by gaboxadol gives rise to a very different MEG signature from the synaptic action of zolpidem. Tiagabine theoretically can affect both types of receptor; from these MEG results it is likely that the latter is the more prominent effect here.
authors.affiliation: Division of Brain Sciences, Centre for Neuropsychopharmacology, Imperial College London, UK. Electronic address: d.nutt@imperial.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Nutt
authors.affiliation: Division of Brain Sciences, Centre for Neuropsychopharmacology, Imperial College London, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Division of Brain Sciences, Centre for Neuropsychopharmacology, Imperial College London, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
authors.affiliation: Division of Brain Sciences, Centre for Neuropsychopharmacology, Imperial College London, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Myers
authors.affiliation: Psychopharmacology Unit, School of Social and Community Medicine, University of Bristol, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papadopoulos
authors.affiliation: CUBRIC, School of Psychology, Cardiff University, UK.
authors.forename: Suresh
authors.initials: S
authors.lastname: Muthukumaraswamy
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D058256:Brain Waves / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D015225:Magnetoencephalography; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012146:Rest; D016037:Single-Blind Method; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D000078308:Tiagabine; D055815:Young Adult; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; D007555:Isoxazoles; D009557:Nipecotic Acids; D011725:Pyridines; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem; C015542:gaboxadol; D000078308:Tiagabine
keywords: GABA; Gaboxadol; Human; Magnetoencephalography; Tiagabine; Zolpidem