Effects of tiagabine and vigabatrin on GABA uptake into primary cultures of rat cortical astrocytes.
Tiagabine (TGB) and vigabatrin (VGB) are two novel anticonvulsant compounds reported to exert their pharmacological effects via an action on the gamma-aminobutyric acid (GABA) system. We have investigated the effects of acute exposure of these drugs on the uptake of GABA into rat cortical astrocytes in primary culture. Astrocytes were prepared from the cerebral cortices of one day-old rat pups by a mechanical dissociation technique and were assayed for GABA uptake activity after 21 days in culture. Tiagabine (100-300 nM) and VGB (100 microM) reduced GABA uptake when compared to control at four hours post-exposure. GABA uptake was also reduced following eight and 24 hour exposures to 200 nM TGB. A combination of TGB (200 nM) and VGB (100 microM) treatments reduced GABA uptake when compared to both control and VGB treated cultures. These results support the efficacy of TGB as a GABA uptake inhibitor and suggest that VGB may also exert an effect by this mechanism.
Leach
J P
JP
Epilepsy Research Unit, University Department of Medicine, Western Infirmary, Glasgow, U.K.
Sills
G J
GJ
Majid
A
A
Butler
E
E
Carswell
A
A
Thompson
G G
GG
Brodie
M J
MJ
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000078308:Tiagabine; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D000927:Anticonvulsants; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D000078308:Tiagabine