Effects of Vigabatrin (γ‐vinyl GAB A) on Neuro transmission‐Related Amino Acids and on GAB A nd Benzodiazepine Receptor Binding in Rats

Summary: The effect of 12‐day intraperitoneal i.p. administration of vigabatrin (GVG, γ‐vinyl GAB A) 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 gluta‐mate 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.

[1]  E. Perucca,et al.  Vigabatrin in the treatment of epilepsy: a long-term follow-up study. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[2]  C. Loeb,et al.  Vigabatrin in complex partial seizures: a long-term study , 1989, Epilepsy Research.

[3]  R. Mattson,et al.  A multicentre study of vigabatrin for drug-resistant epilepsy. , 1989, British journal of clinical pharmacology.

[4]  T. Halonen,et al.  Cerebrospinal fluid GABA and seizure control with vigabatrin. , 1989, British journal of clinical pharmacology.

[5]  M. Dam,et al.  Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy. , 1989, British journal of clinical pharmacology.

[6]  T. Halonen,et al.  Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy — a CSF study , 1988, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[7]  P. Riekkinen,et al.  Effect of vigabatrin (gamma-vinyl GABA) on amino acid levels in CSF of epileptic patients. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[8]  T. Halonen,et al.  Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with γ-vinyl GABA (vigabatrin) , 1988, Epilepsy Research.

[9]  E. Mervaala,et al.  Effect of vigabatrin on epilepsy in mentally retarded patients , 1988, Neurology.

[10]  F. Fonnum,et al.  Regulation of Transmitter γ‐Aminobutyric Acid (GABA) Synthesis and Metabolism Illustrated by the Effect of γ‐Vinyl GABA and Hypoglycemia , 1988 .

[11]  A. Ylinen,et al.  Double‐Blind Dose Reduction Study of Vigabatrin in Complex Partial Epilepsy , 1987, Epilepsia.

[12]  W. Löscher,et al.  One to three day dose intervals during subchronic treatment of epileptic gerbils with gamma-vinyl GABA: anticonvulsant efficacy and alterations in regional brain GABA levels. , 1987, European journal of pharmacology.

[13]  T. Halonen,et al.  Somatostatin, β-endorphin, and prolactin levels in human cerebrospinal fluid during the γ-vinyl-GABA treatment of patients with complex partial epilepsy , 1987, Neuropeptides.

[14]  G. Tunnicliff,et al.  Regulation of γ-aminobutyric acid synthesis in the vertebrate nervous system , 1986, Neurochemistry International.

[15]  L. Tuomisto,et al.  Vasopressin levels in the cerebrospinal fluid in rats of different age and sex. , 1986, Neuroendocrinology.

[16]  M. Dam,et al.  Long‐term study of gamma‐vinyl GABA in the treatment of epilepsy , 1985, Acta neurologica Scandinavica.

[17]  A. Sjoerdsma,et al.  Biochemical and clinical effects of γ‐vinyl GABA in patients with epilepsy , 1984, Neurology.

[18]  C. Marescaux,et al.  Increased gamma-aminobutyric acid (GABA), homocarnosine and β-alanine in cerebrospinal fluid of patients treated with γ-vinyl GABA (4-amino-hex-5-enoic acid) , 1981 .

[19]  S. Kish,et al.  γ‐VINYL GABA: EFFECTS OF CHRONIC ADMINISTRATION ON THE METABOLISM OF GABA AND OTHER AMINO COMPOUNDS IN RAT BRAIN , 1979, Journal of neurochemistry.

[20]  N. M. Gelder.  Taurine, the compartmentalized metabolism of glutamic acid, and the epilepsies. , 1978 .

[21]  N. V. van Gelder.  Taurine, the compartmentalized metabolism of glutamic acid, and the epilepsies. , 1978, Canadian journal of physiology and pharmacology.

[22]  P. Schechter,et al.  γ‐VINYL GABA (4‐amino‐hex‐5‐enoic acid), A NEW SELECTIVE IRREVERSIBLE INHIBITOR OF GABA‐T: EFFECTS ON BRAIN GABA METABOLISM IN MICE 1 , 1977, Journal of neurochemistry.

[23]  P. Schechter,et al.  Audiogenic seizure protection by elevated brain GABA concentration in mice: Effects of γ-acetylenic GABA and γ-vinyl GABA, two irreversible GABA-T inhibitors , 1977 .

[24]  B. Metcalf,et al.  4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. , 1977, European journal of biochemistry.

[25]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.