Behavioral effects of vigabatrin correlated with whole brain gamma-aminobutyric acid metabolism in audiogenic sensitive rats.
The present study evaluates dose-dependent behavioral effects of acutely or subacutely administered single doses of vigabatrin (gamma-vinyl gamma-aminobutyric acid, gamma-vinyl GABA, CAS 60643-86-9) in audiogenic sensitive rats, in correlation with whole brain GABA metabolism. There was a discrepancy in timing between behaviorally observed maximal antiepileptic protection (4 h after i.p. administration of gamma-vinyl GABA) and on the other hand maximal inhibition of GABA-transaminase activity and maximal increase of whole brain GABA content (24 h after i.p. administration of gamma-vinyl GABA). This suggests that the antiepileptic properties of gamma-vinyl GABA not only depend on GABA-ergic neurotransmission. A possible explanation is a gamma-vinyl GABA-induced decrease of excitatory amino acids or increased glycine concentrations in the brain.
Department of Neurology and Memory Clinic, Algemeen Ziekenhuis Middelheim, University of Antwerp, Belgium.
S
S
Engelborghs
B A
BA
Pickut
R
R
D'Hooge
P
P
Wiechert
K
K
Haegele
P P
PP
De Deyn
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000378:metabolism*; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin