Hypnotic effect of thalidomide is independent of teratogenic ubiquitin/proteasome pathway

Dangerous drug could lead to safe sleeping pills

29 March 2021

The sleep-promoting effects of thalidomide involve a different molecular pathway than the one responsible for the drug’s most notorious side effect, a mouse study has found.

Thalidomide was once used to treat morning sickness in pregnant women until it was found to cause birth defects. Thalidomide’s toxicity occurs because of the drug’s binding to a protein called cereblon, a key regulator of the cell’s rubbish-disposal system.

Now, a team led by researchers at the University of Tsukuba in Japan has found that it may be possible to chemically modify the drug such that it does not interfere with foetal development but keeps its anti-insomnia benefits.

Using mice that produced a thalidomide-resistant version of cereblon, the researchers found that the drug still enhanced sleep — in particular, a desirable type of slumber known as non-REM sleep. This indicates that thalidomide’s sleep-promoting effects are independent of cereblon. Future thalidomide-like agents that avoid cereblon-binding entirely could thus offer a safe option for treating insomnia.

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References

1. PNAS 117, 23106–23112 (2020). doi: 10.1073/pnas.1917701117