Zebrafish larvae help develop appetite suppressants

Many drugs that take effect in the brain have unwanted side effects, with the appetite suppressant Rimonabant removed from the market due to causing anxiety, depression or suicidal thoughts. This is why researchers want to find active substances that trigger only one very specific behaviour, without any unwanted side effects.

Now, researchers at the University of Zurich and Harvard University have developed a strategy that quickly helps filter out active substances with side effects. They didn’t only look at biochemical tests, instead using zebrafish larvae. Around four millimetres long, these larvae have a biology that is well characterized and can be bred quickly in large quantities, according to the University of Zurich.

The researchers established an automated measuring process to analyze the behavior of several thousand larvae at the same time. This involved feeding fluorescent paramecia to the fish to quantify their feeding behaviour, while similar methods were used for a number of other behaviours. Experiments with known active substances confirmed that the system works.  

The scientists searched for appetite modulators and determined the effects of more than 10,000 small molecules on the behavior of larval zebrafish, with the biological mechanisms of 22 of the most promising substances next tested on mice. There, they had the same effect: compared to existing appetite modulators, they were more selective and had fewer side effects.    

“As far as we know, there are no comparable psychoactive molecules that have such a strong and specific effect as the ones we tested,” commented researcher Josua Jordi, who was involved in the study. The researchers now want to use the new method to look for further psychoactive substances such as antidepressants. To pursue these approaches, Jordi and some of his fellow researchers established the startup EraCal Therapeutics, headquartered in Zollikon in the canton of Zurich.