It turns out that the class of antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, have many effects on human cells.
In a report published in the August 2010 issue of Genetics, researchers used yeast cells to identify secondary drug targets or pathways affected by SSRIs. Such secondary pathways could help explain why different people taking the same drug may experience different effects, and could also lead to new types of drugs altogether.
“We hope that our study begins to illuminate the full breadth of pharmacological effects of antidepressants on cellular physiology starting with the simple unicellular eukaryote, budding yeast,” said Ethan O. Perlstein, Ph.D, a researcher involved in the work from the Lewis-Sigler Institute for Integrative Genomics at Princeton University in New Jersey. “Furthermore, our work validates the notion that simple model organisms may be useful for the study of complex human disease.”
Aware that the antidepressant sertraline (Zoloft) is toxic to yeast cells in large quantities, scientists applied a lethal dose to millions of yeast cells and focused on a few that became resistant to the medication. Researchers then identified the underlying mutations in those cells and applied genetic, biochemical, and electron microscopic imaging techniques to characterize the resistance on a molecular level. Their results suggest that SSRIs actually may affect several cell processes, including nonprotein targets such as phospholipid membranes.
Additionally, the study’s results demonstrate that sertraline targets intracellular membranes and modulate pathways involved in vesicle trafficking that are present in both yeast and human cells. Vesicle trafficking plays an important role in how neural synapses develop and function. More work is necessary, however, to determine the exact clinical relevance of this secondary drug target.
“There’s no question that SSRIs help thousands of people with mental health problems, but there is still some mystery about how they help us,” said Mark Johnston, editor in chief of the journal Genetics. “This study is a key first step toward giving us a comprehensive answer to how SSRIs work, and it may open doors to entirely new therapies.”