N-Benzyltryptamine showsaffinity for theserotonin5-HT2 receptors.[3] Its affinities (Ki) were 245nM for the serotonin5-HT2A receptor, 100nM for the serotonin5-HT2B receptor, and 186nM for the serotonin5-HT2C receptor.[3] In terms of activational activities, specificallycalcium mobilization,N-benzyltryptamine'sEC50Tooltip half-maximal effective concentration (EmaxTooltip maximal efficacy) values were 162nM (62%) at the serotonin 5-HT2A receptor and 50nM (121%) at the serotonin 5-HT2C receptor.[3] At the serotonin 5-HT2A receptor, it had higher affinity than tryptamine, but lower activational potency in comparison.[3] In other studies, at the rat serotonin 5-HT2A receptor,N-benzyltryptamine'sEC50 was 407nM and itsEmax was 26%.[4][5][6]
N-Benzyltryptamine was first described in thescientific literature by Roger W. Brimblecombe and colleagues by at least 1964.[7]Derivatives ofN-benzyltryptamine, such as5-MeO-T-NBOMe, have subsequently been described as well.[8][9][10]
^abcdeBrimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds".Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144.ISBN978-0-85608-011-1.OCLC2176880.OL4850660M.[...] behavioural changes are produced in animals by tryptamines which contain relatively bulky N-substituents (Brimblecombe, 1967), the most potent being N-benzyltryptamine (4.5); this compound was effective in raising rabbit rectal temperature at a dose three times that of N,N-dimethyltryptamine and it also induced LSD-like behaviour in rats placed in the open field situation at doses of 0.5 mg./kg. (s.c.). The drug has not been tested in man and nothing is known about its metabolism. It may well be comparatively resistant to oxidative deamination, although it is odd that the corresponding N,N-dibenzyl derivative (4.6), which is more toxic than the monobenzyl compound, is virtually inactive in these behavioural situations. Possibly the molecule is too bulky to fit easily to a potential hallucinogenic receptor.
^abcdBrimblecombe RW (September 1967). "Hyperthermic effects of some tryptamine derivatives in relation to their behavioural activity".Int J Neuropharmacol.6 (5):423–429.doi:10.1016/0028-3908(67)90034-2.PMID6055322.
^Silva M (2009).Theoretical study of the interaction of agonists with the 5-HT2A receptor (PhD.). Universität Regensburg.Table 5.1: Agonistic potency (pEC50) and intrinsic activity (Emax) of 5-HT2AR partial agonistic arylethylamines (indole, methoxybenzene and quinazolinedione derivatives) used in the study. [...] [Compound] 199 [...]
^Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants".Chem Rev.124 (1):124–163.doi:10.1021/acs.chemrev.3c00375.PMID38033123.Interestingly, a study around a series of N-benzylated-5- methoxytryptamine analogues (Figure 7C) revealed that benzyl substitution led to compounds with very high affinity at the 5-HT2 family receptors.151 Various substituents on the phenyl group were well tolerated, but ortho and meta substitutions generally provided more potent compounds compared to the para substituted analogues (57−66, Figure 7C). Among them, compounds 65 (2-OMe) and 59 (3-OMe) displayed strong affinity at the h5-HT2AR (Ki = 1.51 and 1.05 nM, respectively; [ 125I]-DOI) as very potent partial agonists in the calcium flux assay (EC50 = 1.9 nM (Emax = 81%) and 6.2 nM (Emax = 52%), respectively). More importantly, compounds 65 and 59 were also tested in the HTR experiment, and they exhibited potent hallucinogenic effects with ED50 values of 3.15 nM and 3.28 nM, respectively.151
^Halberstadt AL, Geyer MA (2018)."Effect of Hallucinogens on Unconditioned Behavior"(PDF).Behavioral Neurobiology of Psychedelic Drugs. Curr Top Behav Neurosci. Vol. 36. pp. 159–199.doi:10.1007/7854_2016_466.ISBN978-3-662-55878-2.PMC5787039.PMID28224459. Archived fromthe original(PDF) on 2017-08-29. Retrieved2025-06-14.A series of N-benzyl derivatives of 5-methoxytryptamine have been characterized (Table 2). Although several N-benzyl-5-methoxytryptamines produce the HTR, none of the compounds are particularly potent (Nichols et al. 2015). In contrast to the N-benzylphenethylamines, where compounds with an orthosubstituted benzyl group were the most active, activity in the Nbenzyl-5-methoxytryptamines was linked to the presence of a meta-substituent. Almost all the meta-substituted N-benzylated-5-methoxytryptamines were active, including compounds with 3-methyl, 3-methoxy, 3-fluoro, 3-chloro, 3-bromo, and 3-iodo groups (see Table 2). With the exception of the 2-methoxy-substitued compound (5MT-NB2OMe), which elicited the HTR with an ED50 of 3.15 mg/kg (9.08 lmol/kg), none of the compounds with ortho- or para-substituted benzyl groups produced a response at doses up to 30 mg/kg. [...] Table 2 Head twitch response induced by N-benzyl-5-methoxytryptamines [...]
