N-Benzyltryptamine

N-Benzyltryptamine
Clinical data
Other namesT-NB; NB-T
Drug classSerotonin receptor modulator; Serotonin 5-HT2 receptor agonist
ATC code
  • None
Identifiers
  • N-benzyl-2-(1H-indol-3-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.036.196
Chemical and physical data
FormulaC17H18N2
Molar mass250.345 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)CNCCC2=CNC3=CC=CC=C32
  • InChI=1S/C17H18N2/c1-2-6-14(7-3-1)12-18-11-10-15-13-19-17-9-5-4-8-16(15)17/h1-9,13,18-19H,10-12H2
  • Key:PRRZWJAGZHENJJ-UHFFFAOYSA-N

N-Benzyltryptamine, also known as T-NB or NB-T, is a serotonin receptor modulator of the tryptamine family.[1][2] It is the N-benzyl derivative of tryptamine.[1][2]

The drug shows affinity for the serotonin 5-HT2 receptors.[3] Its affinities (Ki) were 245 nM for the serotonin 5-HT2A receptor, 100 nM for the serotonin 5-HT2B receptor, and 186 nM for the serotonin 5-HT2C receptor.[3] In terms of activational activities, specifically calcium mobilization, N-benzyltryptamine's EC50Tooltip half-maximal effective concentration (EmaxTooltip maximal efficacy) values were 162 nM (62%) at the serotonin 5-HT2A receptor and 50 nM (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's EC50 was 407 nM and its Emax was 26%.[4][5][6]

The drug has been reported to produce serotonergic psychedelic-like effects in early studies in animals.[1][2][7] This included hyperthermia and behavioral changes in the open field test.[1][2][7] However, N-benzyltryptamine is not known to have been tested in humans, and it is unknown whether it may produce hallucinogenic effects in humans.[1]

N-Benzyltryptamine was first described in the scientific literature by Roger W. Brimblecombe and colleagues by at least 1964.[7] Derivatives of N-benzyltryptamine, such as 5-MeO-T-NBOMe, have subsequently been described as well.[8][9][10]

See also

References

  1. ^ a b c d e Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. [...] 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.
  2. ^ a b c d Brimblecombe 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. PMID 6055322.
  3. ^ a b c d 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. Bibcode:2019PLoSO..1409804T. doi:10.1371/journal.pone.0209804. PMC 6328172. PMID 30629611.
  4. ^ Silva ME, Heim R, Strasser A, Elz S, Dove S (January 2011). "Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor". J Comput Aided Mol Des. 25 (1): 51–66. doi:10.1007/s10822-010-9400-2. PMID 21088982.
  5. ^ 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 [...]
  6. ^ Heim R (28 February 2010). Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts (Thesis) (in German). Berlin: Freie Univ. Tab. 3-10. 5-HT2A-Rezeptoraktivität der N-Benzyl-2-(1H-indol-3-yl)ethylamin-Derivate 199 – 207, untersucht an 5-HT2ARezeptoren der isolierten Rattenschwanzarterie [...] [Compound:] 199 [...]
  7. ^ a b c Brimblecombe RW, Downing DF, Green DM, Hunt RR (August 1964). "Some Pharmacological Effects of a Series of Tryptamine Derivatives". Br J Pharmacol Chemother. 23 (1): 43–54. doi:10.1111/j.1476-5381.1964.tb01565.x. PMC 1703950. PMID 14206268.
  8. ^ 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. PMID 38033123. 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
  9. ^ 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. ISBN 978-3-662-55878-2. PMC 5787039. PMID 28224459. 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 [...]
  10. ^ Nichols DE, Sassano MF, Halberstadt AL, Klein LM, Brandt SD, Elliott SP, Fiedler WJ (July 2015). "N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues". ACS Chem Neurosci. 6 (7): 1165–1175. doi:10.1021/cn500292d. PMC 4505863. PMID 25547199.



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