Skip to main content
SpringerLink
Log in

Vigabatrin: Ein wirksames Antiepileptikum für bisher pharmakoresistente fokale Epilepsien

  • Conference paper
Vigabatrin

  • 25 Accesses

Zusammenfassung

Seit der Einführung der Valproinsäure 1963 wurde in Deutschland kein neues Antiepileptikum mehr zugelassen. Mit den derzeit verfügbaren Antiepileptika werden insgesamt lediglich ca. 42% vorher unbehandelter Patienten mit einer fokalen Epilepsie anfallsfrei (Smith et al. 1987). Auf der dringenden Suche nach neuen Antiepileptika hat der inhibitorische Neurotransmitter γ-Aminobuttersäure (GABA) große Bedeutung erlangt, da er eine entscheidende Rolle in der Regulation von epileptischen Anfällen spielen soll. Vigabatrin (γ-vinyl-GABA), das dem Neurotransmitter GABA strukturell sehr ähnelt, hemmt die GABA-Trans-aminase selektiv und irreversibel. Die Irreversibilität der Hemmung der GABA-Transaminase, die den Abbau von GABA zu Succinylaldehyd bewirkt, wird durch eine Alkylierung des aktiven Enzymzentrums bewirkt. Die Aktivität des Enzyms steigt somit ausschließlich durch Resynthese an. Vigabatrin bewirkt so einen dosisabhängigen Anstieg der GABA-Konzentration im ZNS und ist in verschiedenen Tierepilepsiemodellen effektiv. Es konnte gezeigt werden, daß eine Einmaldosis von Vigabatrin zu einem Anstieg der GABA-Konzentration im Gehirn von Versuchstieren (Schechter 1986) und im Liquor von Epilepsiepatienten für mindestens 5 Tage führte (Ben-Menachem et al. 1988).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 84.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  • Aicardi J, Arzimanoglu A, Beaumont D (1987) Gamma-vinyl GABA (GVG) for childhood epilepsy: A pilot study. Abstract. 17. Int Epilepsiekongr, Jerusalem, Sept. 1987

    Google Scholar 

  • Bayer A, Zrenner E, Ried S, Schmidt D (1990) Effects of anticonvulsant drugs on retinal function. Psychophysical and electrophysiological findings in patients with epilepsy. Invest Ophthalmol Vis Sci (Suppl):2100

    Google Scholar 

  • Bayer A, Zrenner E, Paulus W (1991) Colour vision deficiences induced by the anticonvulsants phenytoin and carbamazepine. In: Drum B, Moreland JD, Serra A (eds) Colour vision deficiences X. Kluwer, Dordrecht, pp 599–604

    Chapter  Google Scholar 

  • Ben-Menachem E, Persson I, Schechter P, Haegele KD, Huebert N, Hardenburg J, Dahlgren L, Mumford J (1988) Effects of single doses of vigabatrin on CSF concentration of GABA, homocarnosine, homovanillic acid and 5-hydroxy-indolacetic acid in patients with complex partial epilepsy. Epilepsy Res 2:96–101

    Article  CAS  Google Scholar 

  • Besser R, Krämer G, Thümler R (1989) Vigabatrin bei therapieresistenten Epilepsien -Vorläufige Ergebnisse. Akt Neurol 16:89–92

    Article  Google Scholar 

  • Browne TR, Mattson RH, Penry JK, Smith DB, Treimann DM, Wilder BJ, Ben-Menachem E, Napoliello J, Sherry KM, Szabo GK (1987) Vigabatrin for refractory complex partial seizures. Multicenter single-blind study with long-term follow-up. Neurology 37:184–189

    PubMed  CAS  Google Scholar 

  • Cocito L, Maffini M, Perfumo P, Roncallo F, Loeb C (1989) Vigabatrin in complex partial seizures: a long term study. Epilepsy Res 3:160–166

    Article  PubMed  CAS  Google Scholar 

  • Ehinger B (1985) Retinal circuitry and clinical ophthalmology. Biol Bull 168:333–349

    Article  CAS  Google Scholar 

  • Frey HH (1985) Tolerance and dependence, In: Frey HH, Janz D (eds) Antiepileptic Drugs, Handbook of Experimental Pharmacology, Vol 74. Springer, Berlin Heidelberg New York Tokyo, p265

    Google Scholar 

  • Gram L, Blatt Lyon B, Dam M (1983) Gamma-vinyl-GABA: A single-blind trial in patients with epilepsy. Acta Neurol Scand 68:34–39

    Article  PubMed  CAS  Google Scholar 

  • Gram L, Klosterskow P, Dam M (1985) Gamma-vinyl-GABA: A double-blind placebo-controlled trial in partial epilepsy. Ann Neurol 17:262–266

    Article  PubMed  CAS  Google Scholar 

  • Hufschmidt A, Dichgans J, Mauritz KH, Hufschmidt M (1980) Some methods and parameters of body sway quantification and their neurological applications. Arch Psychiat Ner-venkr 228:135–150

    Article  CAS  Google Scholar 

  • Johnston SJ (1990) Letter. Lancet 335:605

    Google Scholar 

  • Kauerz M, Carvajal M (1990) Antiepileptische Prophylaxe mit Gamma-Vinyl-GABA. Langzeitstudie über drei Jahre — kritische Wertung von Behandlungsergebnissen. In: Wolf P (Hrsg) Epilepsie 89. Einhorn, Reinbek, S.401–405

    Google Scholar 

  • Loiseau P, Hardenberg JP, Pestre M, Guyot M, Schechter PJ, Tell GP (1986) Double blind placebo-controlled study of vigabatrin in drug resistant epilepsy. Epilepsia 27:115–120

    Article  PubMed  CAS  Google Scholar 

  • Löscher W, Schwark WS (1985) Development of tolerance to the anticonvulsant effect of diazepam in amygdala-kindled rats. Exp Neurol 90:373

    Article  PubMed  Google Scholar 

  • Löscher W, Frey HH (1987) 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. Eur J Pharmacol 143:335

    Article  PubMed  Google Scholar 

  • Löscher W, Jäckel R, Müller F (1989) Anticonvulsant and proconvulsant effects of inhibitors of GABA degradation in the amygdala-kindling model. Eur J Pharmacol 163:1–14

    Article  PubMed  Google Scholar 

  • Matilainen R, Pitkänen A, Ruutiainen T, Mervaala E, Riekkinen P (1989) Vigabatrin in epilepsy in mentally retarded patients. Br J Clin Pharmacol 27:113–118

    Google Scholar 

  • Mugnini E, Oertel WH (1985) An atlas of the distribution of GABA-ergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In: Björklund A, Hökfeldt T (eds) Handbook of chemical neuroanatomy, Vol 4. Elsevier, Amsterdam, pp 436–607

    Google Scholar 

  • Nagai T, McGeer PL, Araki M, McGeer EG (1984) GABA-T intensive neurons in the rat brain. In: Björklund A, Hökfeldt T, Kuhar MJ (eds) Handbook of chemical neuroanatomy, Vol 3. Elsevier, Amsterdam, pp247–271

    Google Scholar 

  • Otto FG, Egli M (1990) Wirkung von gamma-vinyl-GABA auf partielle Anfälle verschiedener Lokalisation. Abstract, 30. Jahrestagung der Deutschen Sektion der Internationalen Liga gegen Epilepsie, Berlin, Oktober

    Google Scholar 

  • Pedersen SA, Klosterkow P, Gram L, Dam M (1985) Long term study of gamma-vinyl GABA in the treatment of epilepsy. Acta Neurol Scand 72:295–298

    Article  PubMed  CAS  Google Scholar 

  • Perlmann JI, Specht CS, Hidayat AA, Ralph RA, Matta CS (1990) Recurrent keratonus. A study of two cases with light and electron microscopy. ARVO Invest Opthalmol Vis Sci 31:2186

    Google Scholar 

  • Ried S, Schmidt D (1992) Vigabatrintherapie bei pharmakoresistenten fokalen Epilepsien -eigene klinische Erfahrungen. Akt Neurol 19 (Suppl 1):41–45

    Article  Google Scholar 

  • Rimmer EM, Richens A (1984) Double-blind study of gamma-vinyl GABA in patients with refractory epilepsy. Lancet 1:189–190

    Article  PubMed  CAS  Google Scholar 

  • Rimmer EM, Richens A (1989) Interaction between vigabatrin and phenytoin. Br J Clin Pharmacol 27:27–33

    Google Scholar 

  • Rosenberg HC, Chiu TH, Tietz EJ (1986) Studies on the mechanism of tolerance to benzodiazepines, In: Frey HH, Fröscher W, Koella WP, Meinardi H (eds) Tolerance to beneficial and adverse effects of antiepileptic drugs. Raven, New York, p 53

    Google Scholar 

  • Schechter PJ (1986) Vigabatrin. In: Meldrum BS, Porter RJ, (eds) New antiepileptic drugs. Libbey, London, pp 265–276

    Google Scholar 

  • Schechter PJ, Tranier Y, Jung MJ, Bohlen P (1977) Audiogenic seizure protection by elevated brain GABA concentration in mice: Effects of gamma-acetylenic GABA and gamma-vinyl GABA, two irreversible GABA-T inhibitors. Eur J Pharmacol 45:319–328

    Article  PubMed  CAS  Google Scholar 

  • Sivenius J, Ylinen A, Murros K, Matilainen R, Riekkinen P (1987) Double blind dose reduction study of vigabatrin in complex partial epilepsy. Epilepsia 28:1688–1692

    Article  Google Scholar 

  • Smith DB, Mattson RH, Cramer J, Collins JF, Novelly RA, Craft B and the V.A. Epilepsy Cooperative Study Group (1987) Results of a nationwide veterans administration cooperative study comparing the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin and primidone. Epilepsia 28 (suppl):50–58

    Article  Google Scholar 

  • Tartara A, Manni R, Galimberti CA, Hardenberg J, Orwin J, Perucca E (1986) Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study. Epilepsia 27:717–723

    Article  PubMed  CAS  Google Scholar 

  • Tassinari CA, Michelucci R, Ambrosetto G, Salvi F (1987) Double-blind study of vigabatrin in the treatment of drug-resistent epilepsy. Arch Neurol 44:907–910

    Article  PubMed  CAS  Google Scholar 

  • Teeters JL, Eeckmann FH, Lukasiewicz PD, Maguire GW, Eliasof SD, Maple BR, Werblin FS (1990) A computational model of change sensitive inhibition in ganglion cells of the salamander retina. ARVO Invest Opthalmol Vis Sci 31:570

    Google Scholar 

Download references

Authors
  1. S. Ried
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Th. Lempert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Bayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. R. G. Stodieck
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Zrenner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Schweizerische Epilepsie-Klinik, Bleulerstraße 60, CH-8008, Zürich, Switzerland

    Günter Krämer

  2. Arbeitsgruppe Epilepsieforschung, Goethestraße 5, D-14163, Berlin, Germany

    Dieter Schmidt

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ried, S., Lempert, T., Bayer, A., Stodieck, S.R.G., Zrenner, E., Schmidt, D. (1994). Vigabatrin: Ein wirksames Antiepileptikum für bisher pharmakoresistente fokale Epilepsien. In: Krämer, G., Schmidt, D. (eds) Vigabatrin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77131-6_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-77131-6_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-54865-2

  • Online ISBN: 978-3-642-77131-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation