A study demonstrated the role of the serotonin 1B receptor in appetite and showed that triptan, a commonly prescribed migraine medicine, may be repurposed for appetite suppression and obesity.
A daily dose of triptan led obese mice to eat less food and lose weight, suggesting that the migraine medication may also be useful in treating obesity, according to a study published in the Journal of Experimental Medicine.
Triptans, which are commonly prescribed as treatments for acute migraines and cluster headaches, work by targeting the serotonin 1B receptor (Htr1b). Serotonin, a chemical messenger found throughout the brain and body, is known to play a role in appetite. There are 15 different serotonin receptors that sense serotonin and signal for cells to change their behavior in response.
Researchers have previously struggled to understand the role of serotonin receptors in appetite. Additionally, previous drugs that target individual receptors, such as fen-phen and lorcaserin (Belviq), to address appetite have been withdrawn from the market because of adverse effects.
However, the serotonin 1B receptor (Htr1b) has not been well studied in the context of appetite and weight loss before this study, according to study leader Chen Liu, PhD, assistant professor of Internal Medicine and Neuroscience and an investigator in the Peter O’Donnell Jr. Brain Institute.
Researchers at UT Southwestern tested 6 prescription triptans in obese mice that were fed a high-fat diet for 7 weeks. Mice who had been fed 2 of these drugs ate about the same amount over the course of a month; however, mice who had been fed the other 4 triptans ate less.
Weight loss or gain was measured at 24 days. Mice administered a daily dose of the drug frovatriptan lost 3.6% of their body weight on average, whereas mice not given triptan had gained an average of 5.1% of their body weight.
Similar results were observed when the researchers implanted devices into the mice that gave them a steady does of frovatriptan for 24 days.
“We found that these drugs, and one in particular, can lower body weight and improve glucose metabolism in less than a month, which is pretty impressive,” Liu said.
The researchers then sought to determine exactly how frovatriptan impacts food intake and weight by engineering mice to lack either Htr1b or Htr2c, the serotonin receptor targeted by other drugs such as fen-phen and lorcaserin. Frovatriptan no longer decreased appetite or caused weight loss in mice without Htr1b.
There was no effect on frovatriptan’s ability to decrease appetite or cause weight loss in mice lacking Htr2c. Researchers concluded that the drug worked by targeting the serotonin 1B receptor.
“This finding could be important for drug development,” Liu said. “We not only shed light on the potential to repurpose existing triptans but also brought attention to Htr1b as a candidate to treat obesity and regulate food intake.”
The researchers also identified exactly which neurons in the brain were most important for the role of Hrt1b in mediating appetite, identifying a small group of cells in the brain’s hypothalamus. As for why the longer-term impacts of triptans on appetite and weight lost have not previously been reported, Liu suggests that patients would not have noticed these impacts due to triptans generally being prescribed for short-term use.
“We’ve shown that there is real potential to repurpose these drugs, which are already known to be safe, for appetite suppression and weight loss,” concluded study leader Chen Liu, PhD, assistant professor of Internal Medicine and Neuroscience and an investigator in the Peter O’Donnell Jr. Brain Institute.
Researchers show effectiveness of migraine drug in weight loss. Science Daily website. https://www.sciencedaily.com/releases/2022/07/220711163214.htm. Published July 11, 2022. Accessed July 13, 2022.