Drugs with glutamate-based mechanisms of action in psychiatry.

Summary

Standard psychiatric medications work by altering serotonin, dopamine, or norepinephrine, but they often act slowly and lose effectiveness over time, leading to treatment resistance. A growing body of evidence suggests that drugs targeting glutamate receptors can produce rapid, robust, and lasting therapeutic effects, potentially overcoming these limitations. This review covers glutamate-modulating drugs, their mechanisms, and preclinical and clinical studies. Ketamine shows rapid and long-lasting effects. Memantine and minocycline are supported for major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts may improve depressive symptoms. Glutamate-based drugs are promising for treatment-resistant mental disorders, but more research is needed on safety, dosage, and interactions.

Study at a glance

Abstract

Psychopharmacotherapy of major psychiatric disorders is mostly based on drugs that modulate serotonergic, dopaminergic, or noradrenergic neurotransmission, either by inhibiting their reuptake or by acting as agonists or antagonists on specific monoamine receptors. The effectiveness of this approach is limited by a significant delay in the therapeutic mechanism and self-perpetuating growth of treatment resistance with a consecutive number of ineffective trials. A growing number of studies suggest that drugs targeting glutamate receptors offer an opportunity for rapid therapeutic effect that may overcome the limitations of monoaminergic drugs. In this article, we present a review of glutamate-modulating drugs, their mechanism of action, as well as preclinical and clinical studies of their efficacy in treating mental disorders. Observations of the rapid, robust, and long-lasting effects of ketamine and ketamine encourages further research on drugs targeting glutamatergic transmission. A growing number of studies support the use of memantine and minocycline in major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts yield the potential to ameliorate depressive symptoms in patients with affective disorders. Drugs with mechanisms of action based on glutamate constitute a promising pharmacological group in the treatment of mental disorders that do not respond to standard methods of therapy. However, further research is needed on their efficacy, safety, dosage, interactions, and side effects, to determine their optimal clinical use.