Schizophrenia

The NMDA receptor hypofunction hypothesis and mechanisms to increase NMDA receptor function. (A) NMDA receptor function may be approached by direct activation (GlyT1 inhibtion) or indirect activation by activating GPCRs (M1 and mGluR5) that physically and functionally interact with the NMDA receptor. The binding site of the co-agonist glycine on the NR1 subunit and the the binding site of the co-agonist glutamate on the NR2 subunit are indicated. (B) The structure of GlyT1, a 12-transmem-brane domain Na⁺/Cl⁻ dependent neurotransmitter transporter, is schematized along with the gene structure of GlyT1 and the six major iosforms of GlyT1. See text for details.