Neurochemical actions of vigabatrin and tiagabine alone and in combination in mouse cortex.
1. The effects of repeated administration of the anticonvulsant compounds, vigabatrin (VGB) and tiagabine (TGB), on gamma-aminobutyric acid (GABA) concentration and the activities of GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD) were investigated in mouse cortex. 2. VGB alone increased GABA levels and decreased GABA-T and GAD activities. 3. TGB alone was essentially without effect. 4. Low doses of VGB and TGB in combination increased GABA levels when neither drug had such an effect alone. 5. Despite this observation, this study failed to establish any conclusive evidence for an interaction between VGB and TGB that might help to explain their reported clinical synergism.
Leach
J P
JP
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Sills
G J
GJ
Butler
E
E
Forrest
G
G
Thompson
G G
GG
Brodie
M J
MJ
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000078308:Tiagabine; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D000927:Anticonvulsants; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D020888:Vigabatrin; D000078308:Tiagabine