NEtPhOH-THPI

NEtPhOH-THPI, also known as N′-(2-methoxyphenylethyl)-THPI, is a serotonin 5-HT₂ receptor agonist and possible serotonergic psychedelic of the tetrahydropyridinylindole (THPI) family related to psychedelic tryptamines.^[1] It is a cyclized tryptamine with an NBOMe-like substitution.^[1]

Other namesN′-(2-Methoxyphenylethyl)-THPI; Compound 24c; 3-(1-(2-Methoxyphenylethyl)-1,2,3,6-tetrahydropyridin-5-yl)-1H-indole

Drug classSerotonin 5-HT₂ receptor agonist; Serotonin 5-HT_2A receptor agonist; Serotonergic psychedelic; Hallucinogen

ATC code

• None

FormulaC₂₁H₂₂N₂O

Quick facts Clinical data, Other names ...

NEtPhOH-THPI

Clinical data
Other names	N′-(2-Methoxyphenylethyl)-THPI; Compound 24c; 3-(1-(2-Methoxyphenylethyl)-1,2,3,6-tetrahydropyridin-5-yl)-1H-indole
Drug class	Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code	None
Identifiers
IUPAC name 2-{2-[5-(1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl]ethyl}phenol
Chemical and physical data
Formula	C21H22N2O
Molar mass	318.420 g·mol−1
3D model (JSmol)	Interactive image
SMILES O([H])C1C=CC=CC=1CCN1CC(C2C3C(=CC=CC=3)N([H])C=2)=CCC1
InChI InChI=1S/C21H22N2O/c24-21-10-4-1-6-16(21)11-13-23-12-5-7-17(15-23)19-14-22-20-9-3-2-8-18(19)20/h1-4,6-10,14,22,24H,5,11-13,15H2 Key:FGMLLLJKETXMGK-UHFFFAOYSA-N

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The drug is a potent and high-efficacy partial agonist of the serotonin 5-HT_2A receptor.^[1] Its affinity (K_i) for the receptor was 8.58 nM and its EC₅₀Tooltip half-maximal effective concentration and E_maxTooltip maximal efficacy values were 20.7 nM (66.5%) for G_q signaling and 58.4 nM (80.7%) for β-arrestin2 signaling.^[1] NEtPhOH-THPI is also a potent near-full agonist of the serotonin 5-HT_2B receptor (EC₅₀ = 7.94 nM; E_max = 88.9%) and a lower-potency full agonist of the serotonin 5-HT_2C receptor (EC₅₀ = 263 nM; E_max = 105.1%).^[1] It is a weak serotonin reuptake inhibitor (IC₅₀Tooltip half-maximal inhibitory concentration = 1,288 nM) as well.^[1]

NEtPhOH-THPI induced the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.^[1] It produced the head-twitch response at a dose of 3 mg/kg in mice but not at a dose of 1 mg/kg or 10 mg/kg.^[1] The drug produced about half the maximal number of head twitches as LSD.^[1] The preclinical pharmacokinetics of NEtPhOH-THPI via intraperitoneal injection have been studied.^[1]

NEtPhOH-THPI was first described in the scientific literature by Rongyan Li and colleagues by 2025.^[1] A close non-hallucinogenic pyrrolopyridine analogue with antidepressant-like effects in rodents was also reported.^[1] The chemical syntheses of both this compound and NEtPhOH-THPI were described.^[1]