Enlightening the "Spirit Molecule": Photomodulation of the 5-HT_2A Receptor by a Light-Controllable N,N-Dimethyltryptamine Derivative.

ABSTRACT: Classical psychedelics are a group of hallucinogens which trigger non-ordinary states of consciousness through activation of the 5-HT_2A receptor (5-HT_2A R) in the brain. However, the exact mechanism of how 5-HT_2A R agonism alters perception remains elusive. When studying receptor signaling, tools which work at the same spatiotemporal resolution as the receptor are exceptionally useful. To create such a tool, we designed a set of photoswitchable ligands based on the classical psychedelic N,N-dimethyltryptamine (DMT). By incorporation of the DMT-indole ring into the photoswitchable system, we obtained red-shifted ligands which can be operated by visible light. Among these azo-DMTs, compound 2 h ("Photo-DMT") stands out as its cis isomer exhibits DMT like acti

SUBMITTER: Gerwe H 

PROVIDER: S-EPMC9324199 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature