November 24, 2011
Researchers Help Fight Ineffective Antipsychotic Drugs
Researchers interested in the treatment of schizophrenia and dementia have helped clarify how antipsychotic drugs that target a complex of two receptors at the surface of cells in the brain work.
The team has shown that two brain receptors, which bind the neurotransmitter signals serotonin and glutamate at the outside of the cell, form a complex in the areas of the brain that malfunction in schizophrenic patients.
The researchers have developed a metric that may help determine the effectiveness of antipsychotic drugs and advance drug design.
The work helps fill important gaps in knowledge as previously researchers did not understand how this receptor complex was connected to their phenotype of schizophrenia.
The study findings show that the connections between the complex of the two receptors and the schizophrenic phenotype is a defect in how the serotonin and glutamate signals get interpreted at the inside of the cell.
"Not only have we learned how antipsychotics drugs are effective, but we have also found that the signaling through this receptor complex is critical to how these anti-psychotics work," the study's principal investigator Diomedes E. Logothetis said in a press release.
He said the most common cellular targets for drugs used in the clinics and by the pharmaceutical industry are G protein-coupled receptors.
They found that using cell and animal models, the receptors signal differently when they are together as a complex than when they are apart.
The team's metric they developed could be used to screen new drugs and help determine their level of effectiveness, or be used to assess combination therapies.
"We can use the metric we developed to screen new drugs and determine their level of effectiveness," Logothetis said in a statement. "We can also use the metric to assess what combinations of existing drugs will give us the ideal balance between the signaling through the two receptors of the complex."
He said the hope is that by using this approach one day researchers will be able to develop a means by which high-throughput screening of drugs can be performed and they also will be able to develop more effective combinations of drugs that could help the third of schizophrenic patients who do not respond to current treatments.
The study was published in the journal Cell on Wednesday.
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