Lorcaserin and Cardiovascular Risk?
In addition to the primary objective of weight loss, BLOOM and BLOSSOM phase 3 trials also looked at the drug’s effect on the heart, cardiovascular risk, central fat distribution, mood and other factors. These were necessary investigations because lorcaserin could also activate receptors 5HT2A and 5HT2B. These receptors are activated by serotonin to mediate a number of functions including learning, mood, smooth muscle contraction and inflammation. It was important to assess whether or not lorcaserin may have unintended consequences by affecting these functions.
The way to look at this is to think of lorcaserin as a key that may have the ability to open locks (receptors) that are similar to each other. For example, say you have a car key that can fit the ignition of similar car models. If the engine turns over the car will run (an unintended and unwanted consequence). If it doesn’t quite fit nothing will happen. Arena had to learn if their weight loss drug may affect systems that have nothing to do with appetite. Fortunately, lorcaserin had greater affinity for the 5HT2C receptor (the one that mediates weight loss) meaning that it was less likely to activate the receptors that helped control other functions.
Why was the FDA concerned?
The FDA advisory committee was concerned about lorcaserin’s effect on the cardiovascular, cancer risk, and mental health of consumers. Cancerous tumors in rats was the biggest concern to the advisory panel. It was found that rats that had been administered high doses of lorcaserin developed mammary gland tumors.
Even though Arena speculated that this was caused by a lorcaserin-stimulated prolactin release the FDA was concerned that humans taking lorcaserin may develop cancer. There is also a relationship between serotonin and prolactin which makes it of particular interest to this study which is using a drug (lorcaserin) to mimic serotonin.
Serotonin has been shown to increase prolactin production via a number of receptors including those that maybe activated by lorcaserin. Prolactin is a hormone that has many functions, one of which is facilitating lactation. Although men and women synthesize prolactin its production increases during pregnancy. The hormone has been found to cause breast cancer in some women.