Effects of vigabatrin (gamma-vinyl GABA) on neurotransmission-related amino acids and on GABA and benzodiazepine receptor binding in rats.
The effect of 12-day intraperitoneal i.p. administration of vigabatrin (GVG, gamma-vinyl GABA) to rats on the neurotransmission-related amino acids in various brain regions (cortex, hippocampus, cerebellum, and spinal cord), cisternal fluid (CSF) and blood was studied. Results showed that GVG administration increased the levels of GABA in cortical and subcortical regions of the brain and CSF without affecting GABA and benzodiazepine receptors in the cortex. In addition, a dose-dependent decrease was noted in the concentration of glutamate in the hippocampus and in the concentrations of aspartate and glutamine in the cortex, hippocampus, and cerebellum. The changes in the levels of amino acids in the brain, except for that of GABA, were not reflected in the CSF, however, and the levels of amino acids in discrete brain regions did not show any correlation with those in the serum or in the CSF. The results suggest that GVG administration might suppress development and spread of seizures not only by elevating the level of the inhibitory amino acid GABA, but also by decreasing the levels of excitatory amino acids in the brain.
Halonen
T
T
Department of Neurology, University of Kuopio, Finland.
Pitkänen
A
A
Saano
V
V
Riekkinen
P J
PJ
D000596:Amino Acids / Q000032:analysis / Q000378:metabolism*; D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000517:prevention & control; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D000596:Amino Acids; D000614:Aminocaproates; D000927:Anticonvulsants; D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin