5-Phenoxytryptamine

5-Phenoxytryptamine

Clinical data
Other names	5-Phenyloxytryptamine; 5-PhO-T; OVT2; OVT-2; Otava 3736689
Drug class	Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code	None
Identifiers
IUPAC name 2-(5-phenoxy-1H-indol-3-yl)ethanamine
CAS Number	31363-70-9
PubChem CID	35780
ChemSpider	32912
ChEMBL	ChEMBL5275778
Chemical and physical data
Formula	C16H16N2O
Molar mass	252.317 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC=C(C=C1)OC2=CC3=C(C=C2)NC=C3CCN
InChI InChI=1S/C16H16N2O/c17-9-8-12-11-18-16-7-6-14(10-15(12)16)19-13-4-2-1-3-5-13/h1-7,10-11,18H,8-9,17H2 Key:ZURXROHPCVOMGH-UHFFFAOYSA-N

5-Phenoxytryptamine (5-PhO-T), also known as OVT2 or Otava 3736689, is a psychedelic drug of the tryptamine family related to 5-methoxytryptamine (5-MT; 5-MeO-T). ^{[1] [2]} It is the derivative of tryptamine and 5-methoxytryptamine in which there is a phenoxy group at the 5 position. ^[2] The drug acts as a biased agonist of the serotonin 5-HT_2A receptor, favoring G_αi signaling over G_αq and β-arrestin1 signaling, though not favoring G_αq signaling over β-arrestin2 signaling. ^{[1] [2]} Its affinity (K_i) for the serotonin 5-HT_2A receptor is 57.5 nM and its activational potency at this receptor ranges from 0.28 nM to 15,800 nM and efficacy ranges from 30% to 91% depending on the downstream signaling pathway. ^[2] OTV2, given via intracerebroventricular injection, produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. ^[2] In addition, it produces long-term memory deficits that are dependent on serotonin 5-HT_2A receptor activation in rodents. ^[2] The drug was first described in the scientific literature by Elk Kossatz and colleagues in 2024. ^{[1] [2]}

See also

• Substituted tryptamine
• 5-Benzyloxytryptamine
• BW-723C86

References

1. Jastrzębski MK, Wójcik P, Grudzińska A, Andreozzi G, Vetrò T, Asim A, et al. (September 2025). "Biased signaling via serotonin 5-HT_2A receptor: From structural aspects to in vitro and in vivo pharmacology". Acta Pharmaceutica Sinica. B. 15 (9): 4438–4455. doi: 10.1016/j.apsb.2025.07.002 . PMC   12491688 . PMID   41049744. Likewise, Kossatz et al.71 explored the complex nature of 5-HT2A receptor signaling in response to different signaling probes by using MD simulations followed by in vitro and in vivo studies. They utilized small molecules (for example OTV1 (2-[5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-indol-3-yl]ethan-1-amine), OTV2 (2-(5-phenoxy-1H-indol-3-yl)ethan-1-amine)) and Nitro-I (2-(5-nitro-1H-indol-3-yl)ethamine hydrochloride)) that were close analogs of 5-HT agonists as probes and observed their coupling preferences to provide an insight into the structural basis of functional selectivity. The outcomes showed that the type of ligand interaction with the extracellular loop 2 ECL2 mainly affects the potential of 5-HT2A receptor to activate different G protein subtypes. In addition, small molecules in this study have shown an overall preference for Gαq over Gαi and ß-arrestin subtypes. Interestingly, it was shown that substitutions at position 5 of OTV1 could shift the coupling preferences to Gαi over Gαq. Moreover, different chemical modifications lead to the activation of the preferred G-protein subtype ultimately leading to different physiology responses as well71.
2. Kossatz E, Diez-Alarcia R, Gaitonde SA, Ramon-Duaso C, Stepniewski TM, Aranda-Garcia D, et al. (May 2024). "G protein-specific mechanisms in the serotonin 5-HT_2A receptor regulate psychosis-related effects and memory deficits". Nature Communications. 15 (1) 4307. doi:10.1038/s41467-024-48196-2. PMC   11137019 . PMID   38811567.