The gamma-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats

Eur J Pharmacol. 1992 Sep 22;220(2-3):197-201. doi: 10.1016/0014-2999(92)90748-s.


The effect of systemic administration of the gamma-aminobutyric acid (GABA) uptake inhibitor, R(-)N-(4,4-di(3-methyl-thien-2-yl)-but-3-enyl) nipecotic acid, hydrochloride (tiagabine) (previously NO-328), on extracellular GABA levels in the globus pallidus, ventral pallidum and substantia nigra of awake Sprague-Dawley rats was investigated using in vivo microdialysis. Tiagabine was administered in doses of 11.5 or 21.0 mg/kg i.p. (ED50 and ED85 doses, respectively, for inhibiting pentylenetetrazole-induced tonic seizures). Tiagabine increased the extracellular concentrations of GABA in globus pallidus with peak values 310% of basal level (after 21 mg/kg) and 240% of basal level (after 11.5 mg/kg). A significant increase in extracellular GABA levels was also found in the ventral pallidum (280% increase after 11.5 mg/kg and 350% increase after 21 mg/kg) and in the substantia nigra where the ED85 dose of tiagabine (21 mg/kg) produced a peak value of 200% compared to the basal level. Thus, tiagabine acts as a GABA uptake inhibitor in vivo also.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Globus Pallidus / drug effects
  • Globus Pallidus / metabolism
  • Male
  • Nipecotic Acids / administration & dosage
  • Nipecotic Acids / pharmacology*
  • Pentylenetetrazole / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / prevention & control
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Tiagabine
  • gamma-Aminobutyric Acid / metabolism*


  • Nipecotic Acids
  • gamma-Aminobutyric Acid
  • Pentylenetetrazole
  • Tiagabine