Measuring human brain GABA in vivo: effects of GABA-transaminase inhibition with vigabatrin

Molecular Neurobiology
O A Petroff, D L Rothman

Abstract

Gamma-aminobutyric acid (GABA) plays a pivotal role in suppressing the origin and spread of seizure activity. Low occipital lobe GABA was associated with poor seizure control in patients with complex partial seizures. Vigabatrin irreversibly inhibits GABA-transaminase, raising brain and cerebrospinal fluid (CSF) GABA concentrations. The effect of vigabatrin on occipital lobe GABA concentrations was measured by in vivo nuclear magnetic-resonance spectroscopy. Using a single oral dose of vigabatrin, the rate of GABA synthesis in human brain was estimated at 17% of the Krebs cycle rate. As the daily dose of vigabatrin was increased to up to 3 g, the fractional elevation of brain GABA was similar to CSF increase. Doubling the daily dose from 3 to 6 g failed to increase brain GABA further. Increased GABA concentrations appear to reduce GABA synthesis in humans as it does in animals. With traditional antiepileptic drugs, remission of the seizure disorder was associated with normal GABA levels. With vigabatrin, elevated CSF and brain GABA was associated with improved seizure control. Vigabatrin enhances the vesicular and nonvesicular release of GABA. The release of GABA during seizures may be mediated in part by transporter reversal t...Continue Reading

References

May 11, 1979·Brain Research·P BöhlenM G Palfreyman
Oct 1, 1975·Journal of Neurochemistry·A SellströmA Hamberger
May 1, 1992·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·D L RothmanR G Shulman
Mar 1, 1992·Archives of Neurology·C A van DonselaarA C Declerck
Jun 1, 1991·British Journal of Pharmacology·I Kang, L G Miller
Mar 1, 1991·Neurochemical Research·J D Wood, M Davies
Feb 1, 1991·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·K L Behar, T Ogino
Mar 1, 1991·Neurochemical Research·M G Erlander, A J Tobin
May 1, 1991·Epilepsy Research·A HambergerC Nordborg
Apr 1, 1990·Neurochemical Research·P J Schechter, A Sjoerdsma
Jan 1, 1989·British Journal of Clinical Pharmacology·E Ben-MenachemJ P Mumford
Jan 1, 1989·British Journal of Clinical Pharmacology·P J Schechter
Jan 1, 1989·British Journal of Clinical Pharmacology·L GramA Schousboe
Jan 1, 1989·British Journal of Clinical Pharmacology·J B BoltonA Richens
Jan 1, 1989·British Journal of Clinical Pharmacology·P J RiekkinenA Pitkanen
Jan 1, 1989·Epilepsia·P J RiekkinenT Halonen
Dec 1, 1987·European Journal of Pharmacology·J M MaloteauxA Trouet
Sep 1, 1987·Cellular and Molecular Neurobiology·D L Martin
Mar 1, 1986·Journal of Neurochemistry·J D Wood, H S Sidhu
Mar 1, 1983·Journal of Neurochemistry·H K WardH F Bradford
Oct 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·D L RothmanR G Shulman
Feb 1, 1981·Journal of Neurochemistry·T L PerryS S Gandham
May 1, 1995·Equine Veterinary Journal·J S PriceR G Russell
Jul 1, 1995·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·N B Fountain, E W Lothman
Jul 13, 1995·Nature·M J DuringD D Spencer

❮ Previous
Next ❯

Citations

Jan 16, 2007·Journal of the Association for Research in Otolaryngology : JARO·Thomas J BrozoskiCarol A Bauer
Jan 3, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Brian S Meldrum, Michael A Rogawski
Jul 13, 2001·Pharmacology & Therapeutics·P KwanM J Brodie
Jun 22, 2002·Epilepsy Research·Laura D ErranteOgnen A C Petroff
Jun 18, 2003·Seizure : the Journal of the British Epilepsy Association·Laura D Errante, Ognen A C Petroff
Aug 2, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Helen B SimpsonLawrence S Kegeles
Jan 22, 2003·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·S G MuellerH G Wieser
Jul 7, 2001·Epilepsia·O A PetroffR H Mattson
Nov 24, 1999·BMJ : British Medical Journal·J W PrichardR Turner
Oct 26, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Josie Resende Torres da SilvaWiliam Alves Prado
Jan 24, 2012·AJNR. American Journal of Neuroradiology·L M Levy, A J Degnan
Apr 20, 2005·Drug Discovery Today·Wynne K SchifferStephen L Dewey
Jun 17, 2006·European Journal of Pharmacology·Małgorzata FilipEdmund Przegaliński
Dec 4, 2009·Expert Opinion on Pharmacotherapy·Justin A Tolman, Michele A Faulkner
Dec 7, 2002·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Ognen A C Petroff
Feb 28, 2002·Fundamental & Clinical Pharmacology·E Perucca
Apr 4, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Conny F WaschkiesBasil Künnecke
Feb 11, 2003·NMR in Biomedicine·John W R WelchAndrew M Blamire
Sep 27, 2005·Nature Reviews. Drug Discovery·Ann D KwongKuan-Teh Jeang
Nov 19, 2003·Psychopharmacology Bulletin·Michael J Owens, Charles B Nemeroff
Oct 14, 2005·Journal of Neurophysiology·Anna Floyer-LeaPaul M Matthews
Sep 17, 2019·Reviews in the Neurosciences·Roger D TraubStephen P Hall
Jun 22, 2000·NMR in Biomedicine·V GovindarajuA A Maudsley
Dec 16, 1998·Annals of Neurology·O A PetroffD L Rothman

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Next ❯

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