Selective Strategy Could Lead to New Approaches Against Schizophrenia

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A new class of compounds identified by researchers at Emory University School of Medicine could be developed into drugs for the treatment of schizophrenia. The compounds enhance signaling by molecules in the brain called NMDA receptors, which scientists believe are functioning at low levels in people with schizophrenia.

Led by Stephen Traynelis, PhD, professor of pharmacology, a team of Emory researchers sifted through thousands of chemicals and found one, called CIQ, which could selectively enhance the function of certain NMDA receptors without affecting others.

The results were published Oct. 5, 2010 by the journal Nature Communications.

The first author of the paper is Praseeda Mullasseril, PhD. The research was a collaboration with Dennis Liotta, PhD, professor of chemistry, and his colleagues.

Doctors now treat schizophrenia with a variety of antipsychotic drugs, but these can have several long-term side effects. The rationale for treating schizophrenia via NMDA receptors comes from the observation that when healthy people take the drugs ketamine or phencyclidine (PCP or angel dust), they temporarily experience the symptoms of schizophrenia, such as hallucinations, disorganized thoughts and flattened emotions.

“There is room for improvement in therapeutic treatment of schizophrenia,” Traynelis says. “Exploration of alternative targets, such as the NMDA receptor, could potentially lead to expanded treatment options and improved outcomes for patients with schizophrenia.”

Ketamine and phencyclidine both interfere with NMDA receptors. This has led scientists to the idea that pushing in the opposite direction chemically — enhancing rather than blocking NMDA receptors — may help relieve schizophrenia’s symptoms……

Reported by ScienceDaily
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Emory University, via EurekAlert!, a service of AAAS.
http://www.sciencedaily.com/releases/2010/10/101012114226.htm

Journal Reference: Praseeda Mullasseril, Kasper B. Hansen, Katie M. Vance, Kevin K. Ogden, Hongjie Yuan, Natalie L. Kurtkaya, Rose Santangelo, Anna G. Orr, Phuong Le, Kimberly M. Vellano, Dennis C. Liotta, Stephen F. Traynelis. A subunit-selective potentiator of NR2C- and NR2D-containing NMDA receptors. Nature Communications, 2010; 1 (7): 1 DOI: 10.1038/ncomms1085

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