5-MeO-pyr-T

Last updated

5-MeO-pyr-T
5-MeO-pyr-T.png
Clinical data
Other names5-Methoxy-N,N-tetramethylenetryptamine; 5-Methoxy-3-(2-pyrrolidinoethyl)indole; 1-[2-(5-Methoxy-1H-indol-3-yl)ethyl]pyrrolidine; "Pyrrolidyl-5-methoxytryptamine"; "5-Methoxypyrrolidine-tryptamine"
Routes of
administration 		Oral, smoking [1] [2]
Drug class Serotonin receptor modulator; 5-HT1A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
  • US:Unregulated
Pharmacokinetic data
Duration of action "Several hours" [1]
Identifiers
  • 5-methoxy-3-[2-(pyrrolidin-1-yl)ethyl]-1H-indole
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C15H20N2O
Molar mass 244.338 g·mol−1
3D model (JSmol)
Melting point 164 to 167 °C (327 to 333 °F) (hydrochloride salt)
Boiling point 160 to 170 °C (320 to 338 °F) (freebase at 0.05 mm/Hg)
  • O(c3ccc1c(c(c[nH]1)CCN2CCCC2)c3)C
  • InChI=1S/C15H20N2O/c1-18-13-4-5-15-14(10-13)12(11-16-15)6-9-17-7-2-3-8-17/h4-5,10-11,16H,2-3,6-9H2,1H3 Yes check.svgY
  • Key:KAASYKNZNPWPQG-UHFFFAOYSA-N Yes check.svgY
   (verify)

5-MeO-pyr-T, also known as 5-methoxy-N,N-tetramethylenetryptamine or as 5-methoxy-3-(2-pyrrolidinoethyl)indole, is a serotonin receptor modulator and psychedelic drug of the tryptamine and 5-methoxytryptamine families. [3] [2] It is the 5-methoxy analogue of pyr-T and the derivative of 5-MeO-DMT and 5-MeO-DET in which their N,N-dialkyl groups have been cyclized into a pyrrolidine ring. [3]

Contents

The drug acts primarily as a highly potent serotonin 5-HT1A receptor agonist, with much lower activity at the serotonin 5-HT2A receptor and other serotonin receptors. [4] [5] [6] 5-MeO-pyr-T shows far greater selectivity for the serotonin 5-HT1A receptor than 5-MeO-DMT. [4] [5]

5-MeO-pyr-T was first described in the scientific literature by 1962. [7] [8]

Use and effects

In his book TiHKAL , Alexander Shulgin gives the dose of 5-MeO-pyr-T as 0.5 to 2 mg orally and its duration as "several hours". [1] [2] It was also assessed at doses of 1 to 4 mg smoked. [1]

The drug's effects were dose-dependent and variably included intense tinnitus (ear ringing), nausea and vomiting, miosis (pupil constriction), confusion or cognitive impairment, uncomfortableness, minor dysphoria, partial to complete amnesia, flailing, rolling about, quivering, and shaking, unconsciousness, and prolonged hangover. [1] Reports of psychedelic-like effects were mixed, ranging from producing no closed-eye visuals and none of the "shifting shapes, colors and forms" of dimethyltryptamine (DMT) or clarity/energy of 5-MeO-DMT, to producing a rush, being "intense but not terrifying", initially 5-MeO-DMT-like, ego death, full body buzz, humming resonance, and feeling that "God is love". [1] Other notable comments included "absolute poison", "never again", "very negative", "felt as if the top of my head was blown off", user's actions being scary and others being alarmed, wandering the streets in a fugue state, and the drug being "some weird-ass shit". [1] Its effects have also been described as "white-out" analogously to 5-MeO-DMT and with amplified amnesic effects compared to 5-MeO-DMT. [5] [1]

The effects of 5-MeO-pyr-T appear to be highly variable between individuals. [1] It was described as being very different from other psychedelics and it was emphasized that a trip sitter is essential for 5-MeO-pyr-T. [1] Shulgin has also described 5-MeO-pyr-T as being "not hallucinogenic" and instead as producing "long-lived amnesia and unconsciousness". [2]

Pharmacology

5-MeO-pyr-T shows very high affinity for the serotonin 5-HT1A receptor and much lower affinity or activity at other assessed serotonin receptors. [4] [5] [6] At the serotonin 5-HT1A receptor, it had an affinity (Ki) of 0.577 nM and an activational potency (EC50 Tooltip half-maximal effective concentration) of 2.40 nM. [4] [5] These values were respectively 646-fold and 34-fold more potent than at the serotonin 5-HT2A receptor (Ki = 373 nM, EC50 = 13.5–81.3 nM (depending on assay), Emax Tooltip maximal efficacy = 92%). [4] [5] In other studies, it was a partial agonist of the serotonin 5-HT2A receptor, with an EC50 of 692 nM and an Emax of 73%. [6] In addition, it was a partial agonist of the serotonin 5-HT4 receptor in the rat esophagus, with an EC50 of 355 nM and an Emax of 53%. [6] The drug has also been predicted to bind to the serotonin 5-HT7 receptor, with a predicted affinity (Ki) of 631 nM. [9] In one study, relative to 5-MeO-DMT, 5-MeO-pyr-T had 12-fold greater activational potency at the serotonin 5-HT1A receptor and 3-fold reduced activational potency at the serotonin 5-HT2A receptor, with 38-fold increased selectivity for the serotonin 5-HT1A receptor over the serotonin 5-HT2A receptor. [5]

Besides the serotonin receptors, 5-MeO-pyr-T is very weakly active at the serotonin transporter (SERT). [4] [5] It showed an affinity (Ki) for the SERT of 3,006 nM and an inhibitory potency (IC50 Tooltip half-maximal inhibitory concentration) in terms of serotonin reuptake inhibition of 2,765 nM. [4] Additionally, 5-MeO-pyr-T is a substrate of the SERT and acts as a partial serotonin releasing agent in HEK293 cells, with an EC50 of 5,700 nM. [4] [5]

In early literature, 5-MeO-pyr-T was described as the most potent tryptamine yet evaluated in the open-field test, but as also having high toxicity that would likely preclude evaluation in humans. [3] [7] In subsequent modern studies, 5-MeO-pyr-T produced effects in rodents including the head-twitch response (a behavioral proxy of psychedelic effects), hypothermia, and hypolocomotion. [4] Its median effective dose (ED50) for producing the head-twitch response was slightly higher than that of 5-MeO-DMT (7.29 mg/kg vs. 4.84 mg/kg, respectively), whereas it was much less efficacious in inducing the response compared to 5-MeO-DMT and produced only a weak maximal effect (10.0 events vs. 38.1 events, respectively). [4] 5-MeO-pyr-T was also similarly potent as 5-MeO-DMT in producing hypothermia and hypolocomotion, but conversely showed greater maximal responses for both of these effects. [4]

Chemistry

Analogues

Analogues of 5-MeO-pyr-T (pyrrolidine) with different rings, including 5-MeO-mor-T (morpholine) and 5-MeO-pip-T (piperidine), are also known, but have not been tested in humans. [1] [6]

History

5-MeO-pyr-T was first characterized by Mitzal by 1962. [7] [8] Animal studies were later published by Hunt and Brimblecombe in 1967. [3] [7] The effects of 5-MeO-pyr-T in humans were described by Alexander Shulgin in his book TiHKAL in 1997. [1] Robert Oberlender, from the lab of David E. Nichols at Purdue University, is known to have accidentally taken too high of a dose of 5-MeO-pyr-T and wandered outside in a fugue state. [10] His experience was later included as the highest-dose 5-MeO-pyr-T experience report in TiHKAL. [10] The drug was encountered as a novel designer and recreational drug in Europe by 2017. [4] [11] [12] 5-MeO-pyr-T's pharmacology was more fully characterized in modern studies in 2009, [6] 2023, [5] and 2024. [4]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 Shulgin A, Shulgin A (1997). TiHKAL, The Continuation (1st ed.). Berkeley, CA, USA: Transform Press. pp. 548–551. ISBN   978-0-9630096-9-2 . Retrieved 7 April 2018.
  2. 1 2 3 4 Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN   978-0-12-433951-4.
  3. 1 2 3 4 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. The cyclic analogue of DET, 3-(2-pyrrolidinoethyl)indole (4.13), was as active as the parent compound in behavioural tests in rodents, cats, and primates (Brimblecombe, 1967; Hunt and Brimblecombe, 1967; Brad Icy and Johnston, 1970). The compound was effective at doses down to 0·5 mg./kg. (s.c.) in disrupting the ability of monkeys to perform learned responses, but it is active only at levels which approach its lethal dose and it is unlikely to be tested in man. [...] Compounds of interest which have not been tested in man include [...] 5-methoxy-3-(2-pyrrolidinoethyl)indole, which is the most potent tryptamine so far revealed by the open field test, though its high toxicity will preclude tests in man (Brimblecombe, 1967; Hunt and Brimblecombe, 1967).
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 Puigseslloses P, Nadal-Gratacós N, Ketsela G, Weiss N, Berzosa X, Estrada-Tejedor R, et al. (August 2024). "Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties". Molecular Psychiatry. 29 (8): 2346–2358. doi:10.1038/s41380-024-02506-8. PMC   11412900 . PMID   38486047.
  5. 1 2 3 4 5 6 7 8 9 10 Puigseslloses P, Islam MN, Ketsela G, Holy M, Niello M, Berzosa X, et al. (2023). "5-MeO-MET, 5-MeO-DET and 5-MeO-pyr-T strongly bind to 5-HT1A and 5-HT2A receptors and act as partial SERT substrates". Neuroscience Applied. 2: 103724. doi: 10.1016/j.nsa.2023.103724 .
  6. 1 2 3 4 5 6 Prainer BC (2009). Tryptamin-Derivate als 5-HT4-Rezeptorliganden: Synthese und in-vitro-Pharmakologie [Tryptamine derivatives as 5-HT4 receptor ligands: synthesis and in vitro pharmacology] (Thesis). doi:10.5283/EPUB.12132 . Retrieved 15 June 2025.
  7. 1 2 3 4 Hunt RR, Brimblecombe RW (July 1967). "Synthesis and Biological Activity of Some Ring-Substituted Tryptamines". Journal of Medicinal Chemistry. 10 (4): 646–648. doi:10.1021/jm00316a027. PMID   4962512.
  8. 1 2 Mitzal S (1962). "N/A". Dissertationes Pharm. 14: 305.
  9. ↑ Vermeulen ES, Schmidt AW, Sprouse JS, Wikström HV, Grol CJ (2003). "Characterization of the 5-HT7 Receptor. Determination of the Pharmacophore for 5-HT7 Receptor Agonism and CoMFA-Based Modeling of the Agonist Binding Site". Journal of Medicinal Chemistry. 46 (25): 5365–5374. doi:10.1021/jm030826m. PMID   14640545.
  10. 1 2 Hamilton Morris (22 August 2021). "PODCAST 26: An interview with Vyvanse inventor Dr. Robert Oberlender". The Hamilton Morris Podcast (Podcast). Patreon. Event occurs at 9:44–12:59, 1:16:00–1:32:23, 1:32:24–1:34:32. Archived from the original on 19 August 2022. Retrieved 15 June 2025. [Morris:] Another instance of this would be Oberlender's overdose on 5-methoxypyrrolidine-tryptamine, which I think is one of the most fascinating stories in underground psychedelic scientific research and one that has never been told publicly before this conversation. I don't wanna spoil it, but I think it's an example of how you can look in the scientific literature and you can see oh 5-methoxypyrrolidine-tryptamine, hmmm, it's a potent psychedelic. But until a human being tries it, you don't really know what it is. And this turned out to be quite an unusual molecule. Not a classical psychedelic by any stretch of the imagination. It induces something closer to a dissociative fugue. And I remember reading these reports in TiHKAL and thinking, for one, these reports are not written by Shulgin. [...]
  11. ↑ https://bitnest.netfirms.com/external/EMCDDA/New-Drugs-In-Europe-2017 [ bare URL ]
  12. ↑ https://bitnest.netfirms.com/response/5-MeO-pyr-T-ID-2031-18-report.pdf [ bare URL PDF ]


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