NMDA receptors are brain receptors that are stimulated by glutamate. Poorly functioning NMDA
receptors are thought to be involved in the pathology of schizophrenia. This hypothesis is
based on the observation that PCP, which blocks the NMDA receptor, produces symptoms and
cognitive impairments similar to schizophrenia. Efforts to enhance the function of the NMDA
receptor with glycine and D-cycloserine have met with limited success. An alternative
approach would be to use the drug acamprosate.
Acamprosate, FDA-approved for maintenance of sobriety after detoxification from alcohol,
seems to act through modulation of the NMDA receptor. In the lab, acamprosate has been noted
to act as an antagonist when the NMDA receptors are maximally stimulated but as an agonist
when NMDA receptor stimulation is minimal. This "smart drug" action makes acamprosate
appealing for use in schizophrenia. If acamprosate works as a smart drug in patients, then we
would predict that it would enhance the function of NMDA receptors in schizophrenia and
improve cognition and the symptoms of the illness. Additionally, acamprosate seems to
modulate the NMDA receptor in novel ways distinct from glycine and D-cycloserine.
We will also see if the response to acamprosate differs based on whether participants do or
do not have a past history of alcohol use disorders.
Phase:
Phase 4
Details
Lead Sponsor:
University of Maryland University of Maryland, Baltimore
Collaborators:
National Alliance for Research on Schizophrenia and Depression National Institute on Alcohol Abuse and Alcoholism (NIAAA)