Researchers show effectiveness of migraine medication in weight loss
Triptans, a class of commonly prescribed migraine medications, may also be useful in treating obesity, according to a new study by scientists at UT Southwestern. In a study in obese mice, a daily dose of a triptan caused the animals to eat less and lose weight for a month, the team reported in the Journal of Experimental Medicine.
“We have shown that there is real potential for reusing these drugs, which are already known to be safe, for appetite suppression and weight loss,” said study leader Chen Liu, Ph.D., Assistant Professor of Internal Medicine and Neuroscience and an investigator at the Peter O’Donnell Jr. Brain Institute.
Obesity affects more than 41% of all adults in the US and increases the risk of heart disease, stroke, diabetes, and certain types of cancer. Most treatments for obesity focus on eating habits and physical activity.
Scientists have long known that serotonin, a chemical messenger found throughout the brain and body, plays a key role in appetite. However, there are 15 different serotonin receptors – molecules that sense serotonin and signal cells to change their behavior in response. Researchers have struggled to understand the role of each serotonin receptor in appetite, and previous medications — including fen-phen and lorcaserin (Belviq) — that target specific individual receptors have been pulled from the market due to side effects.
Triptans, which are used to treat acute migraines and cluster headaches, work by targeting a different receptor — the serotonin 1B (Htr1b) receptor — that has not previously been well studied in the context of appetite and weight loss, says Dr. Liu.
For the new study, researchers tested six prescription triptans in obese mice that were fed a high-fat diet for seven weeks. The mice given the two drugs ate the same amount, but the mice fed the other four ate less. After 24 days, mice given a daily dose of the drug frovatriptan lost, on average, 3.6% of their body weight, while mice not given a triptan gained an average of 5.1% of their body weight. Dr Liu and his colleagues saw similar results when they implanted the device into animals that gave them a fixed dose of frovatriptan for 24 days.
“We found that this drug, and one of them, can lose weight and improve glucose metabolism in less than a month, which is quite impressive,” said Dr. Liu.
Because triptans are generally prescribed for short-term use during migraines, Dr. Liu suspects that patients will not be aware of the long-term impact on appetite and weight in the past.
To determine exactly how frovatriptan impacts food intake and body weight, the researchers engineered mice to lack either Htr1b or Htr2c, serotonin receptors targeted by phen-phen and lorcaserin. In mice without Htr1b, frovatriptan no longer decreased appetite or caused weight loss, whereas stopping Htr2c had no effect. This confirms that the drug works by targeting the serotonin 1B receptor.
“These findings may be important for drug development,” said Dr. Liu. “We not only described the potential to reuse existing triptans but also looked at Htr1b as a candidate for treating obesity and regulating food intake.”
The team went on to pinpoint which neurons in the brain are most important for Htr1b’s role in mediating appetite, housing a small group of cells within the brain’s hypothalamus.
Other researchers who contributed to the study include Li Li, Steven C. Wyler, Luis A. León-Mercado, Baijie Xu, Swati, Xiameng Chen, Rong Wan, and Amanda G. Arnold from UT Southwestern; Youjin Oh and Jong-Woo Sohn of the Korea Institute of Advanced Science and Technology; Lin Jia from UT Dallas; Guanlin Wang of the University of Oxford; Katherine Nautiyal of Dartmouth College; and René Hen of Columbia University.
The study was funded by the National Institutes of Health (R01 DK114036, DK130892, F32DK116427, K01AA024809), the American Health Association (16SDG27260001), the UTSW Pilot and Feasibility Award, and the Grossman Endowment Award for Excellence in Diabetes Research.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with outstanding clinical care and education. The institute’s faculty has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. A full-time faculty of more than 2,900 are responsible for innovative medical advances and are committed to rapidly translating science-driven research into new clinical treatments. UT Southwestern doctors provide care in more than 80 specialties to more than 100,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits per year.
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