RT Journal Article
T1 5-HT2 receptor binding, functional activity and selectivity in N-benzyltryptamines
A1 Toro Sazo, Miguel
A1 Brea Floriani, José Manuel
A1 Loza García, María Isabel
A1 Cimadevila Fondevila, Marta
A1 Cassels, Bruce K.
K1 N-benzyltryptamines
K1 5-HT2 receptor
AB The last fifteen years have seen the emergence and overflow into the drug scene of “superpotent” N-benzylated phenethylamines belonging to the “NBOMe” series, accompanied bynumerous research articles. Although N-benzyl substitution of 5-methoxytryptamine isknown to increase its affinity and potency at 5-HT2 receptors associated with psychedelicactivity, N-benzylated tryptamines have been studied much less than their phenethylamineanalogs. To further our knowledge of the activity of N-benzyltryptamines, we have synthesized a family of tryptamine derivatives and, for comparison, a few 5-methoxytryptamineanalogs with many different substitution patterns on the benzyl moiety, and subjected themto in vitro affinity and functional activity assays vs. the human 5-HT2 receptor subtypes. Inthe binding (radioligand displacement) studies some of these compounds exhibited onlymodest selectivity for either 5-HT2A or 5-HT2C receptors suggesting that a few of them, withaffinities in the 10–100 nanomolar range for 5-HT2A receptors, might presumably be psychedelic. Unexpectedly, their functional (calcium mobilization) assays reflected very differenttrends. All of these compounds proved to be 5-HT2C receptor full agonists while most ofthem showed low efficacy at the 5-HT2A subtype. Furthermore, several showed moderateto-strong preferences for activation of the 5-HT2C subtype at nanomolar concentrations.Thus, although some N-benzyltryptamines might be abuse-liable, others might representnew leads for the development of therapeutics for weight loss, erectile dysfunction, drugabuse, or schizophrenia
PB PLOS
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21403
UL http://hdl.handle.net/10347/21403
LA eng
NO Toro-Sazo M, Brea J, Loza MI, Cimadevila M, Cassels BK (2019) 5-HT2 receptor binding, functional activity and selectivity in N-benzyltryptamines. PLoS ONE 14(1): e0209804. https://doi.org/10.1371/journal.pone.0209804
NO This work was supported by FONDECYT (Chile) regular research grants 1110146 and 1150868 to BKC and CONICYT doctoral grant 21140358 to MT-S
DS Minerva
RD 24 abr 2026