Zusammenfassung
Die Entdeckung des Vorkommens von γ-Aminobuttersäure (GABA) und ihrer herausragenden Funktion als inhibitorischer Neurotransmitter im Zentralnervensystem erfolgte in den 50er Jahren (Awapara et al. 1950; Roberts u. Frankel 1950; Elliot u. Florey 1956; Bazemore et al. 1957; Kuffler u. Edwards 1957). Verminderte Konzentrationen von GABA im Zentralnervensystem wurden schon früh mit Epilepsie in Verbindung gebracht (Meldrum 1989). Die im Tiermodell gemachte Beobachtung, daß epileptische Krämpfe durch intraventrikuläre Injektion von GABA zum Stillstand kamen (Hayashi 1958), zeigte, daß bei einer Erhöhung der Gehirnkonzentration des Neurotransmitters GABA antikonvulsive Effekte zu erwarten wären. Jedoch schied eine direkte Verabreichung von GABA selbst, soweit medizinisch akzeptabel, aus, weil GABA die Blut-Hirn-Schranke nicht überwindet (van Gelder u. Elliot 1958). Ein Weg, die GABA-Konzentration im Gehirn anzuheben, war mittels Hemmung des wichtigsten für GABA-Abbau verantwortlichen Enzyms, der GABA-Aminotransferase, gegeben.
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Literatur
Applegate CD, Burchfiel JL (1988) Microinjections of GABA agonists into the amygdala complex attenuates kindled expression in the rat. Exp Neurol 102:185–189
Ariëns EJ (1984) Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur J Clin Pharmacol 26:663–668
Aw apara J, Landua AJ, Fuerst R, Seale B (1950) Free γ-aminobutyric acid in brain. J Biol Chem 187:35–39
Bazemore AW, Elliot KAC, Florey E (1957) Isolation of factor I. J Neurochem 1:334–339
Ben-Menachem E, Persson L, Schechter PJ, Haegele KD, Huebert N, Hardenberg J, Dahlgren L, Mumford JP (1988) Effects of single doses of vigabatrin on CSF concentrations of GABA, homocarnosine, homovanillic acid and 5-hydroxyindoleacetic acid in patients with complex partial epilepsy. Epilepsy Res 2:96–101
Ben-Menachem E, Persson L, Schechter PJ, Haegele KD, Huebert N, Hardenberg J, Dahlgren L, Mumford JP (1989 a) The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients. Brit J Clin Pharmacol 27:79S–85S
Ben-Menachem E, Persson L, Schechter PJ, Haegele KD, Huebert N, Hardenberg J (1989 b) Cerebrospinal fluid parameters in healthy volunteers during serial lumbar punctures. J Neurochem 52:632–635
Ben-Menachem E, Persson LI, Mumford J, Haegele KD, Huebert N (1991) Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid. J Child Neurol 6 (Suppl. 2):S11–S16
Bernasconi R, Klein M, Martin P, Christen P, Hafner T, Partet C, Schmutz M (1988) γ-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. J Neural Transm 72:213–233
Bonhaus DW, McNamara JO (1988) Anticonvulsant action of intranigral γ-vinyl-GABA: role of noradrenergic neurotransmission. Brain Res 438:391–394
Browne TR, Mattson RH, Napoliello MJ, Penry JK, Smith DB, Treiman DM, Wilder BJ (1983) Multicenter single-blind study of gamma-vinyl-GABA for refractory complex partial seizures. Epilepsia 24:521
Dam M (1991) Vigabatrin in refractory epilepsy in adults and its application in children. J Child Neurol 6 (Suppl 2):S25–A29
Danzin C, Jung MJ (1984) Lack of stringent stereospecificity in the inactivation of pyridoxal phosphate-dependent enzymes by suicide-substrates. In: Evangelopoulos AE (ed) Chemical and biological aspects of vitamin B6 catalysis, A. Liss, New York, pp 377–385
De Biase D, Barra D, Bossa F, Pucci P, John RA (1991) Chemistry of the inactivation of 4-aminobutyrate aminotransferase by the antiepileptic drug vigabatrin. J Biol Chem 266:20056–20061
Elliot KAC, Florey E (1956) Factor I. Inhibitory factor from brain. Assay Conditions in brain. Simulating and antagonizing substances. J Neurochem 1:181–192
Frisk-Holmberg M, Kerth P, Meyer P (1989) Effect of food on the absorption of vigabatrin. Brit J Clin Pharmacol 27:23S–25S
Gelder NM van, Elliot KAC (1958) Disposition of γ-aminobutyric acid administered to mammals. J Neurochem 3:139–143
Gram L, Lyon BB, Dam M (1983) Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy. Acta Neurol Scand 68:34–39
Gram L, Klosterskov P, Dam M (1985) Gamma-vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy. Ann Neurol 17:262–266
Gram L, Larsson OH, Johnsen A, Schouesboe A (1989) Experimental studies of the influence of vigabatrin on the GABA system. Brit J Clin Pharmacol 27 (Suppl 1):13S–17S
Grove J, Schechter PJ, Tell G, Koch-Weser J, Sjoerdsma A, Warter JM, Marescaux C, Rumbach L (1981) 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). Life Sci 28:2431–2439
Grove J, Alken RG, Schechter PJ (1984) Assay of γ-vinyl-γ-aminobutyric acid (4-amino-hex-5-enoic acid) in plasma and urine by automatic amino acid analysis. Application to human pharmacokinetics. J Chromatogr 306:383–387
Haegele KD, Schoun J, Alken RG (1983) Determination of the R(-) and S(+)-enantiomers of γ-vinyl-y-aminobutyric acid in human body fluids by gas chromatography-mass spectrometry. J Chromatogr 274:103–110
Haegele KD, Schechter PJ (1986) Kinetics of the enantiomers of vigabatrin after an oral dose of the racemate or the active S-enantiomer. Clin Pharmacol Ther 40:581–586
Haegele KD, Schwartz J-J, Schoun J, Schmitt AH, Schechter PJ (1987) 2-pyrrolidinone in human cerebrospinal fluid: a major constituent of total γ-aminobutyric acid. J Neurochem 49:1402–1406
Haegele KD, Huebert ND, Ebel M, Tell GP, Schechter PJ (1988) Pharmacokinetics of vigabatrin: implications of creatinine clearance. Clin Pharmacol Ther 44:558–565
Haegele KD, (1992) Vigabatrin: Design und Entwicklung eines rational erdachten Therapeutikums. Akt Neurol 19 (Suppl):7-l1
Halonen T, Lehtinen M, Pitkänen A, Ylinen A, Riekkinen PJ (1988) Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with γ-vinyl GABA (vigabatrin). Epilepsy Res 2:246–252
Hayashi T (1959) The inhibitory action of β-hydroxy-γ-aminobutyric acid upon the seizure following stimulation of the motor cortex of the dog. J Physiol 145:570–578
Kuffler SW, Edwards C (1958) Mechanism of gamma aminobutyric acid (GABA) action and its relation to synaptic inhibition. J Neurophysiol 21:589–610
Lippert B, Metcalf BW, Jung MJ, Casara P (1977) 4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. Eur J Biochem 74:441–445
Lippert B, Jung MJ, Metcalf BW (1980) Biochemical consequences of reactions catalyzed by GAD and GABA-T. Brain Res Bull 5 (Suppl 2):375–379
Loiseau P, Hardenberg JP, Pestre M, Guyot M, Schechter PJ, Tell GP (1986) Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy. Epilepsia 27:115–120
Löscher W, Schmidt D (1988) Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res 2:145–181
Marescaux C, Micheletti G, Vergnes M, Rumbach L, Warter J-M (1985) Diazepam antagonizes gabamimetics in rats with spontaneous petit mal-like epilepsy. Eur J Pharmacol 113:19–24
Meldrum BS (1989) GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Brit J Clin Pharmacol 27:3S–11S
Meldrum B, Horton R (1978) 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 59:47–50
Meldrum BS, Murugaiah K (1983) Anticonvulsant action in mice with sound-induced seizures of the optical isomers of γ-vinyl GABA. Eur J Pharmacol 89:149–152
Metcalf BW (1979) Inhibitors of GABA metabolism. Biochem Pharmacol 28:1705–1712
Miller JW, McKeon AC, Ferrendelli JA (1987) Functional anatomy of pentylenetetrazol and electroshock seizures in the rat brainstem. Ann Neurol 22:615–621
Nanavati SM, Silverman RB (1991) Mechanisms of inactivation of γ-aminobutyric acid aminotransferase by the antiepilepsy drug γ-vinyl GABA (vigabatrin). J Am Chem Soc 113:9341–9349
Pitkänen A, Halonen T, Ylinen A, Riekkinen P (1987) Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy. Neuropeptides 9:185–195
Rémy C, Favel P, Tell G, Hardenberg J, Schechter PJ (1986) Etude en double aveugle contre placebo en permutations croisées du vigabatrin dans l’épilepsie de l’adulte résistant à la thérapeutique. Boll Lega It Epil 54/55:241–243
Rey E, Pons G, Richard MO, Vauzelle F, D’Athis P, Chiron C, Dulac O, Beaumont D, Olive G (1990) Pharmacokinetics of the individual enantiomers of vigabatrin (γ-vinyl GABA) in epileptic children. Brit J Clin Pharmacol 30:253–257
Reynolds EH, Ring HA, Farr IN, Heller AJ, Elwes RDC (1991) Open, double-blind and long-term study of vigabatrin in chronic epilepsy. Epilepsia 32:530–538
Riekkinen PJ, Pitkänen A, Halonen T, Lehtinen M, Ylinen A, Sivenius J (1988) Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy — A CSF study. Prog Neuro-Psycho-pharmacol Biol Psychiat 12:81–91
Rimmer EM, Richens A (1984) Double-blind study of γ-vinyl GABA in patients with refractory epilepsy. Lancet 1:189–190
Roberts E, Frankel S (1950) γ-aminobutyric acid in brain: its formation from glutamic acid. J Biol Chem 187:55–63
Schechter PJ: Vigabatrin. In: Meldrum BS, Porter RJ (eds) New anticonvulsant drugs, John Libbey, London 1986 pp265–277
Schechter PJ, Tranier Y, Jung MJ, Bohlen P (1977) Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of γ-acetylenic GABA and γ-vinyl GABA, two irreversible GABA-T inhibitors. Eur J Pharmacol 45:319–328
Schechter PJ, Tranier Y, Grove J (1979) Attempts to correlate alterations in brain GABA metabolism by GABA-T inhibitors with their anticonvulsant effects. Adv Exp Med Biol 123:43–57
Schechter PJ, Hanke NFJ, Grove J, Huebert N, Sjoerdsma A (1984) Biochemical and clinical effects of γ-vinyl GABA in patients with epilepsy. Neurology 34:182–186
Schousboe A, Larsson OM, Seiler N (1986) Stereoselective uptake of the GABA-transaminase inhibitors gamma-vinyl-GABA and gamma-acetylenic GABA into neurons and astrocytes. Neurochem Res 11:1497–1505
Smithers JA, Lang JF, Okerholm RA (1985) Quantitative analysis of vigabatrin in plasma and urine by reversed-phase high-performance liquid chromatography. J Chromatogr 341:232–238
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
Tassinari CA, Michelucci R, Ambrosetto G, Salvi F (1987) Double-blind study of vigabatrin in the treatment of drug-resistant epilepsy. Arch Neurol 44:907–910
Toussi HR, Schatz RA, Waszczak BL (1987) Suppression of methionine sulfoximine seizures by intranigral γ-vinyl GABA injection. Eur J Pharmacol 137:261–264
Tsanaclis LM, Wicks J, Williams J, Richens A (1991) Determination of vigabatrin in plasma by reversed-phase high-performance liquid chromatography. Ther Drug Monitor 13:251–253
Turski L, Cavalheiro EA, Schwarz M, Turski WA, De Moraes Mello LE, Bortolotto ZA, Klockgether T, Sontag KH (1986) Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or γ-vinyl GABA into the substantia nigra. Brain Res 370:294–309
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Haegele, K.D. (1994). Vigabatrin: Design und Entwicklung eines rational erdachten Therapeutikums. In: Krämer, G., Schmidt, D. (eds) Vigabatrin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77131-6_1
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DOI: https://doi.org/10.1007/978-3-642-77131-6_1
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