Central nervous system (CNS) selective amino acid transporters provide an important function in maintaining tonic extracellular levels of amino acids that act as neurotransmitters, synaptic modulators or neurotransmitter precursors. Small molecule inhibitors of these transporters have been postulated and in some cases demonstrated to be useful in the treatment of a range of CNS driven disorders such as epilepsy, anxiety, psychosis, depre-ssion, pain and neurodegenerative disease. Although much of the research to date in this field has focussed on inhibition of the g -amino butyric acid (GABA) transporters more recent reports have also generated interest in modulation of glycine, glutamate and proline transporters. This article will review the current medicinal chemistry literature and structure activity relationships known for mammalian CNS selective amino acid transporters.
Keywords: inhibitors, mammalian central nervous system, amino butyric acid GABA transporters, GAT1, Glycine transporter, proline transporter, taurine transporter, cationic amino acid transporters, glutamate transporters