Bryan L. Roth, M.D., Ph.D., Foundation Scientific Council Member, received a NARSAD Young Investigator Grant in 1992 to study the structure and function of serotonin receptors. At the time, he was having difficulty securing funding for his idea that understanding these receptors would be crucial for the development of safer and more effective psychiatric medications. The NARSAD Grant came at a critical time and allowed him to continue this work when National Institute of Health funding was tight.

Today, as reported in back-to-back papers in Science, he and an international team collaboratively elucidated, with high resolution, the structures of serotonin receptors which are implicated in the actions of many current psychiatric medications. The work offers a valuable framework for designing safer and more effective medications.

“Nearly all psychiatric drugs—including virtually all drugs which treat schizophrenia—affect serotonin receptors to some extent. These receptors also mediate a host of effects outside the brain, for example on blood coagulation, smooth muscle contraction and heart valve growth,” explained Dr. Roth, Professor of Pharmacology at the University of North Carolina School of Medicine (UNC).

Using X-ray crystallography, the team, including scientists from The Scripps Research Institute (TSRI), UNC and the Chinese Academy of Sciences, were able to identify and analyze the high-resolution atomic structures of two kinds of human brain serotonin receptors—known as 5-HT_1B and 5-HT_2B.

The findings will facilitate the development of new, targeted medications that avoid potentially harmful “off-target” effects with greater beneficial actions.

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