Table 2.
Glutamatergic compounds in the treatment of major psychiatric disorders.
| Glutamatereceptors | Compounds | Mechanisms | Target diseases | Examples of ClinicalTrials.gov Identifier(C: completed; T: terminated) |
|---|---|---|---|---|
| iGluR-NMDA | Ketamine | An NMDA antagonist | MDD in alcoholism | NCT01551329 (phase 1) (C) |
| Bipolar depression | NCT01833897 (phase 4) (C) | |||
| Esketamine | An NMDA antagonist | MDD (TRD) | NCT02782104 (phase 3) | |
| Imminent suicide risks | NCT02133001 (phase 2) (C) | |||
| D-cycloserine | Mixed agonist/antagonist at NMDA receptor/glycine binding site | MDD (TRD) | NCT00408031 (phase 2) (C) | |
| Bipolar depression | NCT01833897 (phase 4) (C) | |||
| Schizophrenia | NCT02769936 (phase 1) (C) | |||
| D-serine | An NMDA-glycine site agonist | Schizophrenia | NCT00322023 (phase 2) (C) | |
| RO4917838 (Bitopertin) | A glycine reuptake inhibitor | Schizophrenia | NCT01235585 (phase 3) (C) | |
| NRX-101 | D-cycloserine + lurasidone | Bipolar depression | NCT03395392 (phase 2) | |
| Riluzole | A glutamate release inhibitor | MDD (TRD) | NCT00088699 (phase 2) (C) | |
| Bipolar depression | NCT00054704 (phase 2) (T) | |||
| Nitrous oxide | An NMDA antagonist | MDD (TRD) | NCT02994433 (phase 1) | |
| NMDAE | An NMDA enhancer | MDD | NCT03414931 (phase 2) (C) | |
| Nuedexta | Dextromethorphan+quinidine | MDD (TRD) | NCT01882829 (phase 2) (C) | |
| Dextromethorphan as an NMDA antagonist | ||||
| AXS-05 | Dextromethorphan+bupropion | MDD (TRD) | NCT02741791 (phase 3) | |
| Dextromethorphan as an NMDA antagonist | ||||
| CP-101,606 (traxoprodil) | An NMDA receptor subunit GluN2B Antagonist | MDD (TRD) | NCT00163059 (phase 2) (C) | |
| Memantine | An NMDA antagonist | MDD | NCT00040261 (phase 3) (C) | |
| Sarcosine | An NMDA enhancing agent (a glycine transporter-I inhibitor) | MDD | NCT00977353 (phase 2) (C) | |
| Schizophrenia | NCT01503359 (phase 2) (C) | |||
| AZD6765 | An NMDA channel blocker | MDD (TRD) | NCT00986479 (phase 2) (C) | |
| CERC-301 | An NMDA GluN2B antagonist | MDD | NCT02459236 (phase 2) (C) | |
| MK-0657 | A selective NMDA GluN2B antagonist | MDD (TRD) | NCT00472576 (phase 2) (C) | |
| NRX-1074 | An NMDA partial agonist | MDD | NCT02067793 (phase 2) (C) | |
| GLYX-13 (Rapastinel) | An NMDA receptor enhancer | MDD (TRD) | NCT01684163 (phase 2) (C) | |
| REL-1017 (d-Methadone) | A non-opioid NMDA receptor antagonist | MDD (TRD) | NCT03051256 (phase 2) | |
| EVT-101 | An NMDA GluN2B antagonist | MDD (TRD) | NCT01128452 (phase 2) (T) | |
| iGluR-AMPA | ORG 24448 | an AMPAkine as AMPA receptor potentiators | MDD | NCT00262665 (withdrawn) |
| Schizophrenia | NCT00425815 (withdrawn) | |||
| CX516 | An AMPA receptor positive modulator | Schizophrenia | NCT00235352 (phase 3) (C) | |
| mGluR or other pathways | N-Acetyl-Cysteine (NAC) | May restore glutamate to its correct levels in the brain | Schizophrenia | NCT02505477 (phase 4) |
| MDD (TRD) | NCT02972398 | |||
| Pomaglumetad methionil (LY2140023) | Metabotropic glutamate 2/3 receptor (mGluR2/3R) agonist | Schizophrenia | NCT00149292 (phase 2) (C) | |
| Schizophrenia | NCT01307800 (phase 3) (T) | |||
| JNJ-40411813 (ADX-71149) | mGluR2 positive allosteric modulator | Schizophrenia | NCT01323205 (phase 2) (C) | |
| AZD-8529 | mGluR2 positive allosteric modulator | Schizophrenia | NCT00921804 (phase 2) (C) | |
| RO4995819 (Decoglurant) | GluR2/3 negative allosteric modulator | MDD | NCT01733654 (withdrawn) | |
| Basimglurant | mGluR5 negative allosteric modulator | MDD | NCT01437657 (phase 2) (C) | |
| Diazoxide | Increases glutamate uptake from the synaptic cleft | MDD | NCT02049385 (phase 1) (T) | |
| Ceftriaxone | Decreasing the amount of extracellular glutamate in brain | Schizophrenia | NCT00591318 (phase 1) (T) |