Bitopertin

Bitopertin (RG1678) is an orally available, potent (IC50=30nM) and selective inhibitor of glycine transporter GlyT1. Glycine transporters remove the neurtransmitter glycine from the synapse; their inhibition prolongs glycine transmission. GlyT1 inhibitors increase levels of glycine in the synaptic cleft leading to positive modulation of glutamatergic N-methyl-D-aspartate (NMDA) receptor function since glycine is a co-transmitter at NMDA receptors. Recent reports indicate that hypofunction of NMDA receptors may play an important role in the pathophysiology of schizophrenia, in particular the negative symptoms of the disease. Bitopertin is the first GlyT1 inhibitor to have a beneficial effect in schizophrenic patients.