New antipsychotic drugs may be on horizon

January 29, 2018 GMT

A new and improved class of antipsychotic drugs might be coming our way in the near future, thanks to research funded by the National Institutes of Health.

According to the NIH, the scientists have made a landmark discovery about the widely-prescribed antipsychotic risperidone that could help in the creation of better treatments for schizophrenia, bipolar disorder, and other mental illnesses.

“For the first time, we can understand precisely how atypical antipsychotic drugs bind to their primary molecular target in the human brain,” said Dr. Laurie Nadler, chief of the neuropharmacology program at the National Institute of Mental Health, in a news release. “This discovery opens the way for the rational design of a new generation of antipsychotic drugs, hopefully with more desirable effects and fewer side effects.”

In 2016, a study based off the 2013 Medical Expenditure Panel Survey — which collected data on the cost and use of health care in the U.S. — found that one in six adults reported taking a psychiatric drug.

Researchers Bryan Roth, of the University of North Carolina, Chapel Hill, Brian Shoichet, Ph.D., of the University of California San Francisco, and colleagues, report on their discovery of the crystal structure of the antipsychotic risperidone docked in the D2 dopamine receptor in the journal Nature.

As a psychiatrist, Roth first experienced the limitations of existing antipsychotic medication while treating patients with schizophrenia. According to the NIH the “medications excel at quelling hallucinations and delusions, yet largely fail to address schizophrenia’s debilitating cognitive and social impairments, while increasing risk for movement disorders, weight gain, and other metabolic and cardiovascular side effects.”

Many of these side effects result from existing antipsychotics’ interaction with several other types of receptors, in addition to the D2 receptor. Consequently, an in-depth understanding of the molecular workings holds hope for designing agents with just the desired properties that would act more precisely.

The new molecular pictures show that risperidone binds to the D2 receptor in an unexpected way that could not be predicted based on previous structures of similar dopamine receptors. Notably, the D2 receptor harbors an unexpectedly deep “pocket” that the researchers think could be targeted to design more selective drugs with fewer side effects.