Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms
Major depressive disorder (MDD) is a devastating mental illness that affects approximately 20% of the world’s population. It is a major disease that leads to disability and suicide, causing a severe burden among communities. Currently available medications for treating MDD target the monoaminergic s...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-12-01
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| Series: | General Psychiatry |
| Online Access: | https://gpsych.bmj.com/content/35/6/e100922.full |
| _version_ | 1811203755161419776 |
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| author | Shikai Wang Sufang Tang Jintao Huang Huanxin Chen |
| author_facet | Shikai Wang Sufang Tang Jintao Huang Huanxin Chen |
| author_sort | Shikai Wang |
| collection | DOAJ |
| description | Major depressive disorder (MDD) is a devastating mental illness that affects approximately 20% of the world’s population. It is a major disease that leads to disability and suicide, causing a severe burden among communities. Currently available medications for treating MDD target the monoaminergic systems. The most prescribed medications include selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. However, these medications have serious drawbacks, such as a delayed onset requiring weeks or months to reach efficacy and drug resistance, as one-third of patients are unresponsive to the medications. Therefore, it is imperative to develop novel therapies with rapid action, high efficacy and few adverse effects. The discovery of the rapid antidepressant effect of ketamine has triggered tremendous enthusiasm for studying new antidepressants that target the glutamatergic system in the central nervous system. Many agents that directly or indirectly modulate the glutamatergic system have been shown to provide rapid and lasting antidepressant action. Among these agents, ketamine, an antagonist of metabotropic glutamate 2/3 receptors, and scopolamine, an unspecific muscarinic acetylcholine receptor antagonist, have been extensively studied. In this review, we discuss the clinical and preclinical evidence supporting the antidepressant efficacy of these agents and the current understanding of the underlying mechanisms. |
| first_indexed | 2024-04-12T03:00:32Z |
| format | Article |
| id | doaj.art-3b53a534130a451fa5081bf2462eb54d |
| institution | Directory Open Access Journal |
| issn | 2517-729X |
| language | English |
| last_indexed | 2024-04-12T03:00:32Z |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | General Psychiatry |
| spelling | doaj.art-3b53a534130a451fa5081bf2462eb54d2022-12-22T03:50:41ZengBMJ Publishing GroupGeneral Psychiatry2517-729X2022-12-0135610.1136/gpsych-2022-100922Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanismsShikai Wang0Sufang Tang1Jintao Huang2Huanxin Chen3Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, ChinaHuzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, ChinaHuzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, ChinaHuzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, ChinaMajor depressive disorder (MDD) is a devastating mental illness that affects approximately 20% of the world’s population. It is a major disease that leads to disability and suicide, causing a severe burden among communities. Currently available medications for treating MDD target the monoaminergic systems. The most prescribed medications include selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. However, these medications have serious drawbacks, such as a delayed onset requiring weeks or months to reach efficacy and drug resistance, as one-third of patients are unresponsive to the medications. Therefore, it is imperative to develop novel therapies with rapid action, high efficacy and few adverse effects. The discovery of the rapid antidepressant effect of ketamine has triggered tremendous enthusiasm for studying new antidepressants that target the glutamatergic system in the central nervous system. Many agents that directly or indirectly modulate the glutamatergic system have been shown to provide rapid and lasting antidepressant action. Among these agents, ketamine, an antagonist of metabotropic glutamate 2/3 receptors, and scopolamine, an unspecific muscarinic acetylcholine receptor antagonist, have been extensively studied. In this review, we discuss the clinical and preclinical evidence supporting the antidepressant efficacy of these agents and the current understanding of the underlying mechanisms.https://gpsych.bmj.com/content/35/6/e100922.full |
| spellingShingle | Shikai Wang Sufang Tang Jintao Huang Huanxin Chen Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms General Psychiatry |
| title | Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms |
| title_full | Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms |
| title_fullStr | Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms |
| title_full_unstemmed | Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms |
| title_short | Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms |
| title_sort | rapid acting antidepressants targeting modulation of the glutamatergic system clinical and preclinical evidence and mechanisms |
| url | https://gpsych.bmj.com/content/35/6/e100922.full |
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