A5002202404- Neurotransmitter Receptor Influence on Behavior
- Psychedelics and Drug Studies
- Chemical synthesis and alkaloids
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
Medical College of Wisconsin
2022-2023
Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial agonism several GPCRs, including 5-HT2A, and does not induce head-twitch response (HTR) in mice, supporting its classification a 5-HT2A agonist. Unlike LSD, lacks 5-HT2B agonism, an effect linked to cardiac...
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 recruitment efficacy predicts potential, assessed using head-twitch...
Ariadne is a non-hallucinogenic analog in the phenylalkylamine chemical class of psychedelics that closely related to an established synthetic hallucinogen, 2,5-dimethoxy-4-methyl-amphetamine (DOM), differing only by one methylene group α-position amine. has been tested humans including clinical trials at Bristol-Myers Company indicate lack hallucinogenic effects and remarkable therapeutic effects, such as rapid remission psychotic symptoms schizophrenics, relaxation catatonics, complete...
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 signaling, making their respective roles unclear. To elucidate this, we developed a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 efficacy predicts potential, assessed using head-twitch response (HTR)...