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Scientists ID Pathway That Makes Antipsychotic Drugs Work
Date:8/26/2008

Finding could aid drug manufacturers in development of new therapies

TUESDAY, Aug. 26 (HealthDay News) -- New findings that antipsychotic drugs may not work as scientists have assumed could lead to changes in how the drugs are developed and prescribed, say Duke University Medical Center researchers.

Antipsychotic drugs used to treat schizophrenia and other mental health problems target the D2 receptor inside cells. The Duke researchers found that the biochemical pathways that are linked to this receptor -- and along which the drugs deliver their effects -- may function differently than previously believed.

The Duke team focused on two main pathways linked to the D2 receptor -- the G-protein-dependent signaling pathway and the beta-arrestin pathway. Most antipsychotic drugs target the G-protein signaling that occurs at the D2 receptor. Only recently has beta-arrestin been shown to play a role.

The researchers were surprised by what they found.

"Our work showed that all nine antipsychotic drugs we examined uniformly and more potently block the beta-arrestin pathway downstream of the D2 dopamine receptor," lead author Bernard Masri, a postdoctoral researcher in the department of cell biology, said in a Duke news release.

But the drugs had a range of effects on the G-protein pathway.

"Some activated it, some blocked the G side totally, some blocked it only 50 percent -- the drugs had different profiles for the G-protein pathway," Masri said.

"So, with this new information, drug manufacturers would want to make sure new compounds for antipsychotic use block the beta-arrestin pathway," he noted.

The study was published in this week's issue of the journal Proceedings of the National Academy of Sciences.

More information

The U.S. National Institute of Mental Health has more about

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