Enlightening the "Spirit Molecule": Photomodulation of the 5-HT2A Receptor by a Light-Controllable N,N-Dimethyltryptamine Derivative.
Angewandte Chemie (International ed. in English) June 27, 2022 Hubert Gerwe, Feng He, Eline Pottie et al. 21 citations
Classical psychedelics alter consciousness by activating the 5-HT2A receptor in the brain, but the precise mechanism is not fully understood. To study this receptor's signaling with high spatiotemporal precision, researchers designed photoswitchable ligands based on the psychedelic N,N-dimethyltryptamine (DMT). By incorporating the DMT-indole ring into a photoswitchable system, they created red-shifted ligands operable by visible light. Among these azo-DMTs, compound 2h (Photo-DMT) stands out: its cis isomer shows DMT-like activity, while the trans isomer acts as a weak partial agonist. This cis-on efficacy switch expands the pharmacological toolbox for investigating the complex signaling of the 5-HT2A receptor.