Ketamine, benzoate, and sarcosine for treating depression.

A review compares the antidepressant mechanisms of sarcosine, benzoate, ketamine, esketamine, and arketamine. These compounds modulate N-methyl-d-aspartate glutamate receptors (NMDARs) and reduce brain inflammation by inhibiting microglial activity. Though they act differently as antagonists or coagonists of NMDARs, all have shown efficacy in animal models or human trials. The review concludes that these drugs act as both NMDAR modulators and anti-inflammatory agents, making them potentially effective for treating depression.

Study at a glance

Abstract

Studies have demonstrated the beneficial therapeutic effects of sarcosine, benzoate, and ketamine (including esketamine and arketamine) on depression. These drugs mainly act by modulating N-methyl-d-aspartate glutamate receptors (NMDARs) and reducing inflammation in the brain. Although ketamine, benzoate, and sarcosine act differently as the antagonists or coagonists of NMDARs, they all have demonstrated efficacy in animal models or human trials. In vitro and in vivo studies have indicated that sarcosine, benzoate, and ketamine exert their anti-inflammatory effects by inhibiting microglial activity. This review summarizes and compares the efficacy of the possible therapeutic mechanisms of sarcosine, benzoate, ketamine, esketamine, and arketamine. These compounds act as both NMDAR modulators and anti-inflammatory drugs and thus can be effective in the treatment of depression.