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Design of a new psychedelic quipazine analog with therapeutic efficacy and potentially fewer side effects
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DOI：10.1126/scisignal.adw6055.png)
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Abstract
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The clinical use of serotonergic psychedelics is limited by their side effects. Younkin et al. generated a derivative (called VCU-1012) of the psychedelic quipazine with greater activity at the serotonin receptor subtype that mediates the clinically desirable effects (5-HT2AR) than at the serotonin receptor subtype responsible for the undesirable ones. Similar to quipazine, VCU-1012 exerted antidepressant and antianxiolytic effects in mice but without the gastrointestinal side effects of quipazine. Moreover, like other psychedelics, VCU-1012 increased dendritic spine density in the frontal cortex in a 5-HT2AR–dependent manner. Thus, VCU-1012 shows promise as a 5-HT2AR agonist with a more favorable side effect profile than those of typical psychedelics. —Wei Wong
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