GABA-aminotransferase Inhibitors

GABA, gamma-aminobutyric acid, is the chief inhibitory neurotransmitter in humans. It plays a role in regulating neuronal excitability throughout the nervous system. In humans, GABA is directly responsible for the regulation of muscle tone.

The precise mechanism of action for GABA transaminase or GABA-T (GABA-AT) inhibitors and their antiseizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of the enzyme GABA-AT, which is responsible for the metabolism and degradation of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system.


CPP-109 (vigabatrin) is a first-generation GABA-aminotransferase (GABA-AT) inhibitor. Vigabatrin is already approved for human use (Sabril®, Lundbeck), and Catalyst is employing CPP-109 as a research surrogate for exploring potential indications for which there are no adequate animal models. These conditions include, but are not limited to, PTSD and Tourette’s syndrome.


For more information about (GABA-AT) inhibitors, please choose from the list of clinical publications and reviews below.

Doumlele K, Conway E, Hedlund J, Tolete P, Devinsky O. A case report on the efficacy of vigabatrin analogue (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115) in a patient with infantile spasms. Epilepsy Behav Case Rep. 2016;6:67-69.  Go to publication

Briggs SW, Mowrey W, Hall CB, Galanopoulou AS. CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms. Epilepsia. 2014; 55(1):94-102.  Go to publication

Hawker DD, Silverman RB. Synthesis and evaluation of novel heteroaromatic substrates of GABA aminotransferase. Bioorg Med Chem. 2012;20(19):5763-5773.  Go to publication

Pan Y, Gerasimov MR, Kvist T, et al.  (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent γ-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction.  J Med Chem. 2012;55(1):357-366. Go to publication

Yuan H, Silverman RB. Structural modifications of (1S,3S)-3-amino-4–difluoromethylenecyclopentanecarboxylic acid, a potent irreversible inhibitor of GABA aminotransferase. Bioorg Med Chem Lett.2007;17(6):1651–1654. Go to publication