Science
March 21, 2013
Daniel Wacker, Chong Wang, Vsevolod Katritch et al.
689 citations
Serotonin receptors are targets for drugs treating depression, obesity, and migraine headaches. Crystal structures of two serotonin receptor subtypes bound to antimigraine medications or a precursor of LSD reveal how subtle differences in ligand binding cause substantial differences in receptor signaling and biological responses. The structures show that the same ligand can activate one or both of the two main serotonin receptor signaling mechanisms, depending on which receptor it binds.
Science
March 22, 2013
Chong Wang, Yi Jiang, Jinming Ma et al.
522 citations
Two research teams independently determined the crystal structures of two serotonin receptors bound to antimigraine drugs or a precursor of LSD. The structures show that subtle differences in how ligands bind to these receptors lead to substantial differences in the signals generated and the resulting biological responses. The same ligand can activate one or both of the two main serotonin receptor signaling mechanisms, depending on which specific receptor it binds to.
Beilstein Journal of Organic Chemistry
October 8, 2012
Adam Pigott, Stewart Frescas, John D. Mccorvy et al.
19 citations
Replacing the ethylamine side chain of two psychedelic amphetamine derivatives, DOI and DOB, with a cyclopropylamine moiety produced compounds with high affinity for the 5-HT(2) family of serotonin receptors. The more potent stereoisomer of these cyclopropane analogues had the expected (-)-(1R,2S)-configuration. However, the cyclopropane congeners also showed increased affinity at several other serotonin receptor subtypes beyond 5-HT(2A) and 5-HT(2B). While at appropriate doses the compounds may serve as tools to probe 5-HT(2) receptor function, their selectivity for 5-HT(2A) receptors is somewhat less than that of DOI itself.
Nature Structural & Molecular Biology
June 22, 2026
Qianru Jiang, Jianming Han, Eve Fine et al.
Ketamine, used for treatment-resistant depression and severe pain, acts primarily by blocking the N-methyl-D-aspartate receptor, but its therapeutic and abuse-related effects may involve additional targets. Structural evidence shows that ketamine and its analog phencyclidine (PCP) can directly bind to and activate human opioid receptors. The study identifies key molecular motifs involved in this binding and efficacy modulation, and also reveals the structure of the ligand-free state of the κ opioid receptor. Ketamine exhibits more dynamic binding than PCP at the orthosteric site, which may explain its distinct pharmacology. These findings indicate that opioid receptors are important for understanding ketamine's clinical versatility.
UNC Libraries
October 31, 2020
Adam Pigott, Bryan L. Roth, Xi‐ping Huang et al.
Replacing the ethylamine side chain of the psychedelic compounds DOI and DOB with a cyclopropylamine group produced new molecules that bind strongly to 5-HT2 family serotonin receptors. The most potent version had the (−)-(1R,2S)-configuration. However, these cyclopropane analogs also showed increased affinity for other serotonin receptor subtypes beyond 5-HT2A and 5-HT2B, making them less selective than the original compounds. At appropriate doses, they may serve as research tools for studying 5-HT2 receptor function, but their reduced selectivity for 5-HT2A receptors must be considered.