NEtPhOH-THPI

NEtPhOH-THPI, also known as N′--THPI, is a serotonin 5-HT₂ receptor agonist and possible serotonergic psychedelic of the tetrahydropyridinylindole family related to psychedelic tryptamines. It is a cyclized tryptamine with an NBOMe-like substitution.
The drug is a potent and high-efficacy partial agonist of the serotonin 5-HT_2A receptor. Its affinity for the receptor was 8.58nM and its and values were 20.7nM for G_q signaling and 58.4nM for β-arrestin2 signaling. NEtPhOH-THPI is also a potent near-full agonist of the serotonin 5-HT_2B receptor and a lower-potency full agonist of the serotonin 5-HT_2C receptor. It is a weak serotonin reuptake inhibitor as well.
NEtPhOH-THPI induced the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. It produced the head-twitch response at a dose of 3mg/kg in mice but not at a dose of 1mg/kg or 10mg/kg. The drug produced about half the maximal number of head twitches as LSD. The preclinical pharmacokinetics of NEtPhOH-THPI via intraperitoneal injection have been studied.
NEtPhOH-THPI was first described in the scientific literature by Rongyan Li and colleagues by 2025. A close non-hallucinogenic pyrrolo pyridine analogue with antidepressant-like effects in rodents was also reported. The chemical syntheses of both this compound and NEtPhOH-THPI were described.