Inhibitors of mammalian central nervous system selective amino acid transporters

Central nervous system (CNS) selective amino acid transporters provide an i mportant function in maintaining tonic extracellular levels of amino acids that act as neurotransmitters, synaptic modulators or neurotransmitter prec ursors. Small molecule inhibitors of these transporters have been postulate d and in some cases demonstrated to be useful in the treatment of a range o f CNS driven disorders such as epilepsy, anxiety, psychosis, depression, pa in and neurodegenerative disease. Although much of the research to date in this field has focussed on inhibition of the gamma-amino butyric acid (GABA ) transporters more recent reports have also generated interest in modulati on of glycine, glutamate and proline transporters. This article will review the current medicinal chemistry literature and structure activity relation ships known for mammalian CNS selective amino acid transporters.