Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1988 Nov;51(11):1395–1400. doi: 10.1136/jnnp.51.11.1395

Effect of vigabatrin (gamma-vinyl GABA) on amino acid levels in CSF of epileptic patients.

A Pitkänen 1, R Matilainen 1, T Ruutiainen 1, M Lehtinen 1, P Riekkinen 1
PMCID: PMC1032809  PMID: 2853206

Abstract

Vigabatrin (gamma-vinyl GABA) is a new anticonvulsive drug that irreversibly inhibits the activity of GABA transaminase. The effect of vigabatrin on neurotransmission-related amino acids in CSF of 28 epileptic patients was studied and the relationship between the amino acid pattern and clinical response during 7 months of administration of vigabatrin. Of this study population, 46% had more than 50% decrease in seizure frequency (responders). In 54% the seizures decreased less than 50% (nonresponders). In the whole study group, the levels of total GABA during vigabatrin treatment were 283%, free GABA 197%, homocarnosine 310% and glycine 128% that of the levels at baseline in the same patients. Glutamate, glutamine, aspartate, asparagine, and taurine concentrations did not change. The amino acid pattern in CSF during administration of vigabatrin did not differ significantly in responders and nonresponders. The study suggests that both GABAergic and glycinergic neurotransmission are affected by vigabatrin. The changes in CSF levels of neurotransmitter amino acids are, however, not necessarily related to the clinical response.

Full text

PDF
1395

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Böhlen P., Huot S., Palfreyman M. G. The relationship between GABA concentrations in brain and cerebrospinal fluid. Brain Res. 1979 May 11;167(2):297–305. doi: 10.1016/0006-8993(79)90824-2. [DOI] [PubMed] [Google Scholar]
  2. Engel J., Jr, Brown W. J., Kuhl D. E., Phelps M. E., Mazziotta J. C., Crandall P. H. Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol. 1982 Dec;12(6):518–528. doi: 10.1002/ana.410120604. [DOI] [PubMed] [Google Scholar]
  3. Gale K. Role of the substantia nigra in GABA-mediated anticonvulsant actions. Adv Neurol. 1986;44:343–364. [PubMed] [Google Scholar]
  4. Grove J., Palfreyman M. G., Schechter P. J. Cerebrospinal fluid GABA as an index of brain GABA activity. Clin Neuropharmacol. 1983;6(3):223–229. doi: 10.1097/00002826-198309000-00004. [DOI] [PubMed] [Google Scholar]
  5. Grove J., Schechter P. J., Hanke N. F., de Smet Y., Agid Y., Tell G., Koch-Weser J. Concentration gradients of free and total gamma-aminobutyric acid and homocarnosine in human CSF: comparison of suboccipital and lumbar sampling. J Neurochem. 1982 Dec;39(6):1618–1622. doi: 10.1111/j.1471-4159.1982.tb07995.x. [DOI] [PubMed] [Google Scholar]
  6. Haynes L., Yau K. W. Cyclic GMP-sensitive conductance in outer segment membrane of catfish cones. Nature. 1985 Sep 5;317(6032):61–64. doi: 10.1038/317061a0. [DOI] [PubMed] [Google Scholar]
  7. Jung M. J., Lippert B., Metcalf B. W., Böhlen P., Schechter P. J. gamma-Vinyl GABA (4-amino-hex-5-enoic acid), a new selective irreversible inhibitor of GABA-T: effects on brain GABA metabolism in mice. J Neurochem. 1977 Nov;29(5):797–802. doi: 10.1111/j.1471-4159.1977.tb10721.x. [DOI] [PubMed] [Google Scholar]
  8. Lloyd K. G., Bossi L., Morselli P. L., Munari C., Rougier M., Loiseau H. Alterations of GABA-mediated synaptic transmission in human epilepsy. Adv Neurol. 1986;44:1033–1044. [PubMed] [Google Scholar]
  9. Matilainen R., Pitkänen A., Ruutiainen T., Mervaala E., Sarlund H., Riekkinen P. Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study. Neurology. 1988 May;38(5):743–747. doi: 10.1212/wnl.38.5.743. [DOI] [PubMed] [Google Scholar]
  10. Meldrum B., Horton R. Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid). Psychopharmacology (Berl) 1978 Sep 15;59(1):47–50. doi: 10.1007/BF00428029. [DOI] [PubMed] [Google Scholar]
  11. Mirski M. A., Ferrendelli J. A. Anterior thalamic mediation of generalized pentylenetetrazol seizures. Brain Res. 1986 Dec 10;399(2):212–223. doi: 10.1016/0006-8993(86)91511-8. [DOI] [PubMed] [Google Scholar]
  12. Myslobodsky M. S., Ackermann R. F., Engel J., Jr Effects of gamma-acetylenic GABA and gamma-vinyl GABA on metrazol-activated, and kindled seizures. Pharmacol Biochem Behav. 1979 Sep;11(3):265–271. doi: 10.1016/0091-3057(79)90133-3. [DOI] [PubMed] [Google Scholar]
  13. Pedersen S. A., Klosterskov P., Gram L., Dam M. Long-term study of gamma-vinyl GABA in the treatment of epilepsy. Acta Neurol Scand. 1985 Sep;72(3):295–298. doi: 10.1111/j.1600-0404.1985.tb00873.x. [DOI] [PubMed] [Google Scholar]
  14. Perry T. L., Hansen S. Amino acid abnormalities in epileptogenic foci. Neurology. 1981 Jul;31(7):872–876. doi: 10.1212/wnl.31.7.872. [DOI] [PubMed] [Google Scholar]
  15. Perry T. L., Hansen S., Kennedy J., Wada J. A., Thompson G. B. Amino acids in human epileptogenic foci. Arch Neurol. 1975 Nov;32(11):752–754. doi: 10.1001/archneur.1975.00490530074007. [DOI] [PubMed] [Google Scholar]
  16. Perry T. L., Kish S. J., Hansen S. gamma-Vinyl GABA: effects of chronic administration on the metabolism of GABA and other amino compounds in rat brain. J Neurochem. 1979 Jun;32(6):1641–1645. doi: 10.1111/j.1471-4159.1979.tb02274.x. [DOI] [PubMed] [Google Scholar]
  17. Piredda S., Pavlick M., Gale K. Anticonvulsant effects of GABA elevation in the deep prepiriform cortex. Epilepsy Res. 1987 Mar;1(2):102–106. doi: 10.1016/0920-1211(87)90014-3. [DOI] [PubMed] [Google Scholar]
  18. Pitkänen A., Halonen T., Ylinen A., Riekkinen P. Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy. Neuropeptides. 1987 Apr;9(3):185–195. doi: 10.1016/0143-4179(87)90038-2. [DOI] [PubMed] [Google Scholar]
  19. Riekkinen P. J., Pitkänen A., Halonen T., Lehtinen M., Ylinen A., Sivenius J. Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(1):81–91. doi: 10.1016/0278-5846(88)90063-2. [DOI] [PubMed] [Google Scholar]
  20. Schechter P. J., Hanke N. F., Grove J., Huebert N., Sjoerdsma A. Biochemical and clinical effects of gamma-vinyl GABA in patients with epilepsy. Neurology. 1984 Feb;34(2):182–186. doi: 10.1212/wnl.34.2.182. [DOI] [PubMed] [Google Scholar]
  21. Shin C., Rigsbee L. C., McNamara J. O. Anti-seizure and anti-epileptogenic effect of gamma-vinyl gamma-aminobutyric acid in amygdaloid kindling. Brain Res. 1986 Nov 29;398(2):370–374. doi: 10.1016/0006-8993(86)91498-8. [DOI] [PubMed] [Google Scholar]
  22. Turski L., Cavalheiro E. A., Turski W. A., Meldrum B. S. Excitatory neurotransmission within substantia nigra pars reticulata regulates threshold for seizures produced by pilocarpine in rats: effects of intranigral 2-amino-7-phosphonoheptanoate and N-methyl-D-aspartate. Neuroscience. 1986 May;18(1):61–77. doi: 10.1016/0306-4522(86)90179-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES