Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

The GABA Transporter and its Inhibitors

Author(s): W. Soudijn and I. van Wijngaarden

Volume 7, Issue 10, 2000

Page: [1063 - 1079] Pages: 17

DOI: 10.2174/0929867003374363

Price: $65


GABA is the major inhibitory neurotransmitter in the brain and GABA re- uptake from the synaptic cleft is one important mechanism in the regulation of GABA activity. Inhibition of the re-uptake of GABA by potent and selective inhibitors of the GABA transporter enhances GABA activity. This property can be used therapeutically in for instance epilepsy or psychiatric disorders. In this paper putative structures of the GABA transporter, its mechanism of action, the progress made in the search for its amino acids involved in the binding of substrates and the SAR of inhibitors acting at the transporter will be discussed. To date only highly selective GAT-1 inhibitors are available. These compounds are lipophilic derivatives of (R)-nipecotic acid and guvacine. The most potent inhibitors of the cloned human GAT-1 are NNC-711 (IC50 = 0.04 μM) and tiagabine (IC50 = 0.07 μM). A diheteroarylvinyloxy analogue of tiagabine, 5 times more potent than tiagabine, has been reported recently. For the GAT-2, GAT-3 and BGT-1 subtypes only compounds with a small preference for one of the subtypes have been published.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy