Novel Schizophrenia Treatments Target Glutamate Receptors
the Psychiatry Advisor take:
Antagonism or partial agonism at the dopamine D2 receptor and antagonism at the serotonin 5-HT2A receptor are what most schizophrenia drugs target in the brain. While these medications have been effective, other drugs are typically added to a treatment regimen to deal with negative symptoms or cognitive impairment.
However, new agents are in development for the treatment of schizophrenia. As Leslie Citrome, MD, of the Department of Psychiatry and Behavioral Sciences, New York Medical College, in Valhalla, says, many new treatment on the horizon involve the neurotransmitter glutamate.
Activating glutamate can produce either an increase or decrease in the release of dopamine in the brain, which in turn impacts areas related to the symptoms of schizophrenia.
While both metabotropic and ionotropic glutamate receptors have been researched, Citrome said in Psyclopedia that most schizophrenia drugs under development target MNDA receptors, which have seen positive results in trials.
He also describes a non-glutamate treatment, encenicline (EVP-6124), which is a selective α7 nicotinic acetylcholine (N-A7A) receptor agonist. These receptors are located in brain areas involved in cognitive functions.
“Effective treatments for negative and cognitive symptoms remain an unmet need in schizophrenia management,” Citrome concludes. “Strategies such as combining antipsychotics and adding adjunctive agents to antipsychotics have yielded mostly disappointing results for both of these symptom domains.
“The NMDA receptor hypofunction hypothesis, with its focus on the glutamate system’s effect on dopamine, may potentially explain the positive, negative, and cognitive symptoms of schizophrenia. Therapeutic targets different from those of current antipsychotic agents are actively being investigated. Research includes adjunctive agents that bind to sites on NMDA receptors (glycine, d-serine, d-cycloserine), adjunctive glycine reuptake inhibitors (sarcosine, bitopertin), as well as agents that work through different pathways (encenicline).”
New Drugs in Development to Treat Schizophrenia
Psychiatry Advisor Articles
- Anxiety Prevention Interventions: How Effective Are They?
- ADHD, Comorbid Bipolar Disorder Share Similar Neurocognitive Profiles
- Antidepressant Use and Dementia Risk in the Elderly
- Risk for Adverse Outcomes With Antidepressants in Dementia
- Chronic Alcohol Use Disorder Symptoms Occur Regardless of Social Status
- Suicidal Behavior, Thoughts Associated With Perfectionist Tendencies
- CBT, Acceptance Commitment Therapy Helpful for Those With Chronic Pain
- Physicians Spend Nearly 6 Hours on EHR Tasks Per Day
- Depression Reduced by Social Belonging, Feelings of Inclusion
- Sleep Disturbance May Be Causal Factor in Psychotic Experiences
- Buprenorphine, Methadone Combined With CNS Depressants May Lead to SAEs
- Vagus Nerve Stimulation in HIV-Associated Depression
- Depression Profiles in Patients With Type 1 Diabetes vs Type 2 Diabetes
- Purpose, Questions of Social Interaction Lead Physicians to Delay Retirement
- Retirement Saving Behavior Associated With Psychological Distress