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Pharmacology: Virtual drug scan identifies potential new antidepressants

Nature

2022년9월29일

Two LSD-like chemical molecules are found to have antidepressant effects in mice, without psychedelic side effects, reports a Nature paper. Although further testing is required before they can become drug candidates in humans, the discovery of these molecules could lead to the development of drugs for treating psychiatric disorders in the future.

Psychedelics, such as LSD and psilocybin, are known to target specific serotonin receptors and have been suggested as alternatives for treating psychiatric disorders — including schizophrenia, depression and anxiety. However, whether it is possible to develop these compounds therapeutically without their hallucinogenic activities remains unknown. Developing LSD-like therapeutic drugs without psychedelic activity is an attractive goal for the treatment of psychiatric disorders. Virtual screening is a computational approach for predicting drug activity that can be used to find interesting compounds that target serotonin receptors.

Brian Shoichet, Jon Ellman, Bryan Roth and colleagues created a bespoke virtual library of over 75 million molecules within the family of tetrahydropyridines, which are also found in LSD, and virtually tested them to see whether they interacted with serotonin receptors. They found two molecules that activated serotonin receptors and tested them in mice. These molecules were found to have antidepressant effects in mice without psychedelic effects. Additionally, these molecules were as effective as the antidepressant fluoxetine but at doses 40 times lower. The authors note that these molecules require further investigation and optimization before they can be considered drug candidates.

These findings demonstrate the potential of bespoke screening libraries to identify new drug leads.

doi: 10.1038/s41586-022-05258-z

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