Scientists Discover Intricacies of Serotonin Receptor Crucial for Better Therapeutics
By crystalizing a serotonin receptor bound to several common compounds, UNC School of Medicine scientists discovered how slightly different drugs can cause severe side effects or none at all. The findings should accelerate the design of safer and more effective medications for a variety of conditions.
Serotonin, known as the “happiness” neurotransmitter, is a chemical found in the body responsible for feelings of well-being. But serotonin isn’t the only chemical that binds to the 13 serotonin receptors found on the surface of cells. Far from it. Many approved drugs also bind to serotonin receptors. And one of these receptors – called 5-HT2BR – has made drug developers very unhappy. That’s because some drugs that treat Parkinson’s disease, migraines, pituitary tumors, and obesity were designed to target other cellular receptors but also activate 5-HT2BR, leading to life-threatening valvular heart disease. As a result, many of these drugs have been pulled from the market.
Now, for the first time, UNC School of Medicine scientists have figured out precisely why one drug binds to 5-HT2BR and activates the receptor to cause heart problems while very similar drugs do not. They’ve also discovered why a third drug acts like a 5-HT2BR antagonist – it blocks the receptor’s activity – while the very well-known similar hallucinogenic drug LSD does not.
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