Human brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose

Neurology. 1996 May;46(5):1459-63. doi: 10.1212/wnl.46.5.1459.

Abstract

Using 1H spectroscopy, we measured occipital lobe GABA levels serially in 18 patients enrolled in an ongoing open label trial of vigabatrin. Brain GABA levels were elevated twofold in patients taking vigabatrin (3 to 4 g/d) compared with nonepileptic subjects. Serial measurements suggested that brain GABA rose in proportion to vigabatrin dose up to 3 g/d. Doubling the dose from 3 to 6 g/d failed to increase brain GABA further. Serial measurements on three patients taking 6 g/d showed a gradual decrease in brain GABA in two patients over 1 to 2 years of treatment. These observations suggest that GABA synthesis may decrease at high GABA levels.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism*
  • Dose-Response Relationship, Drug
  • Epilepsy, Complex Partial / drug therapy*
  • Epilepsy, Complex Partial / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrogen
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Occipital Lobe / drug effects
  • Occipital Lobe / metabolism*
  • Time Factors
  • Vigabatrin
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Anticonvulsants
  • gamma-Aminobutyric Acid
  • Hydrogen
  • Vigabatrin