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Researchers at the University of Illinois at Chicago are one step closer to discovering why people are so difficult to withdraw from some antidepressants.
The treatise, “Antidepressants, Lipid Next raft medicine Withdrawal “, published in the journal Molecular pharmacologyIs working on the molecular and cellular mechanisms that cause antidepressant withdrawal syndrome.
The authors of the study, Mark Lasenic, a prominent professor of physiology and biophysics and psychiatry at UIC, a research career scientist at the Jesse Brown VA Medical Center, and Nicholas Senese, a postdoctoral fellow at UIC, He explained that current antidepressants can take about two months to take, and then work for patients who continue to take these drugs for years. Separating the patient from these drugs can cause a variety of unpleasant symptoms, from flu-like sensations and persistent pain and itching to Parkinson’s disease-like conditions that last for weeks.
One in six Americans suffers from depression. For veterans, the estimated rate is twice that.
Previous studies have shown that antidepressants gradually collect in a cholesterol-rich membrane structure called lipid rafts.When neurotransmitters (such as mood-related serotonin) bind to lipid proteins, receptors on the outside of cells raft -Called Gs Alpha-A signal can be transmitted inside the cell, where various actions can be elicited. One of these actions is the production of an intracellular signaling molecule called cyclic AMP. Cyclic AMP is low in the brains of depressed people. However, with effective antidepressant treatment, cyclic AMP returns to normal.
For their new study, Rasenick and Senese used fluorescent lights to study the activity of Gs alpha molecules and determined how to get in and out of lipid rafts. They found that discontinuation of some antidepressants balanced the action of Gs-alpha inside and outside lipid rafts, while others suppressed the return of Gs-alpha to lipid rafts. Researchers believe that this suppression causes long-lasting and unwanted effects of some antidepressants.
Lipid rafts appear to be associated with both delayed therapeutic effects of antidepressants and difficulty withdrawing from these drugs. It takes a long time for these drugs to be classified as rafts, and it takes a long time for them to come out-there are some more than others.Curiously, fast-acting antidepressants like ketamine are called Gsα. Lipid raftBut without delay, Lasenic said.
“This tests the notion that intracellular molecules resulting from active Gs alpha proteins are very good biomarkers for antidepressant function,” Rasenick said. “I think we have some clarity about this issue. We would like to move forward towards using technology to create personalized treatments for depression.”
Rasenick explained that by examining how the cells of individual patients metabolize the Gs alpha protein, it is possible to more accurately predict what antidepressants will work for them. This can be achieved in days, not weeks or months of trial and error to find the right drug. Pax Neuroscience, a company that uses the technology developed by UIC, was founded to develop technology for the market.
Nicolas B. Senese et al, antidepressants, cause sustained Gαs-related signaling changes in lipid rafts after drug withdrawal. Molecular pharmacology (2021). DOI: 10.1124 / molpharm.120.000226
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University of Illinois, Chicago
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