Allosteric modulation of neurotransmitter transporters at excitatory synapses

The regulation of glutamate and glycine concentrations within excitatory synapses plays an important role in maintaining a dynamic signalling process between neurones, but the failure to regulate the concentrations of these neurotransmitters has been implicated in the pathogenesis of various neurological disorders. In this review we shall discuss how glutamate and glycine transporters regulate synaptic concentrations of these neurotransmitters and how endogenous allosteric modulators influence transporter function. Whilst glutamate transport inhibitors are unlikely to be of therapeutic value because their potential to cause excitoxicity and cell death, a greater understanding of how endogenous compounds allosterically modulate glutamate transporters may provide alternate drug targets. On the other hand, there are some promising drugs that inhibit glycine transporters, which are being trialled as an alternate treatment for schizophrenia. We shall discuss how the activity of one such compound may be expected to influence excitatory neurotransmission. (C) 2004 Elsevier B.V. All rights reserved.