作用机理
It is believed that vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase GABA-T) or block the reuptake of GABA into glia and nerve endings. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.
参考文献
A365 - Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. (11752352)
A2119 - Weber OM, Verhagen A, Duc CO, Meier D, Leenders KL, Boesiger P: Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography. Magn Reson Imaging. 1999 Apr;17(3):417-25. (10195585)
A2120 - Valdizan EM, Garcia AP, Armijo JA: Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats. Eur J Pharmacol. 1999 Mar 19;369(2):169-73. (10206175)
A2121 - Arndt CF, Derambure P, Defoort-Dhellemmes S, Hache JC: Outer retinal dysfunction in patients treated with vigabatrin. Neurology. 1999 Apr 12;52(6):1201-5. (10214744)
A2122 - Molina PE, Ahmed N, Ajmal M, Dewey S, Volkow N, Fowler J, Abumrad N: Co-administration of gamma-vinyl GABA and cocaine: preclinical assessment of safety. Life Sci. 1999;65(11):1175-82. (10503933)
A2123 - French JA: Vigabatrin. Epilepsia. 1999;40 Suppl 5:S11-6. (10530689)
A9529 - Pan Y, Qiu J, Silverman RB: Design, synthesis, and biological activity of a difluoro-substituted, conformationally rigid vigabatrin analogue as a potent gamma-aminobutyric acid aminotransferase inhibitor. J Med Chem. 2003 Dec 4;46(25):5292-3. (14640537)
A9530 - Pan Y, Gerasimov MR, Kvist T, Wellendorph P, Madsen KK, Pera E, Lee H, Schousboe A, Chebib M, Brauner-Osborne H, Craft CM, Brodie JD, Schiffer WK, Dewey SL, Miller SR, Silverman RB: (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. J Med Chem. 2012 Jan 12;55(1):357-66. doi: 10.1021/jm201231w. Epub 2011 Dec 30. (22128851)