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| Other names | 5-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 receptoragonist;Serotonergic psychedelic;Hallucinogen |
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| Duration of action | "Several hours"[1] |
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| Formula | C15H20N2O |
| Molar mass | 244.338 g·mol−1 |
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| 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) |
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5-MeO-pyr-T, also known as5-methoxy-N,N-tetramethylenetryptamine or as5-methoxy-3-(2-pyrrolidinoethyl)indole, is aserotonin receptor modulator andpsychedelic drug of thetryptamine,5-methoxytryptamine, andpyrrolidinylethylindole families.[3][2] It is the 5-methoxyanalogue ofpyr-T and thederivative of5-MeO-DMT and5-MeO-DET in which theirN,N-dialkyl groups have beencyclized into apyrrolidinering.[3]
The drug acts primarily as a highlypotentserotonin5-HT1A receptoragonist, with much lower activity at the serotonin5-HT2A receptor and otherserotonin receptors.[4][5][6] 5-MeO-pyr-T shows far greaterselectivity for the serotonin 5-HT1A receptor than 5-MeO-DMT.[4][5]
5-MeO-pyr-T was first described in thescientific literature by 1962.[7][8]
In his bookTiHKAL,Alexander Shulgin gives the dose of 5-MeO-pyr-T as 0.5 to 2 mgorally and itsduration as "several hours".[1][2] It was also assessed at doses of 1 to 4 mgsmoked.[1]
The drug's effects weredose-dependent and variably included intensetinnitus (ear ringing),nausea andvomiting,miosis (pupil constriction),confusion orcognitive impairment, uncomfortableness, minordysphoria, partial to completeamnesia, flailing, rolling about, quivering, and shaking,unconsciousness, and prolongedhangover.[1] Reports ofpsychedelic-like effects were mixed, ranging from producing noclosed-eye visuals and none of the "shifting shapes, colors and forms" ofdimethyltryptamine (DMT) or theclarity orenergy of5-MeO-DMT, to producing arush, 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 afugue 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 atrip sitter is essential for 5-MeO-pyr-T.[1] Shulgin has also described 5-MeO-pyr-T as being "nothallucinogenic" and instead as producing "long-lived amnesia and unconsciousness".[2]
5-MeO-pyr-T shows very highaffinity for theserotonin5-HT1A receptor and much lower affinity or activity at other assessedserotonin receptors.[4][5][6] At the serotonin 5-HT1A receptor, it had an affinity (Ki) of 0.577 nM and anactivationalpotency (EC50Tooltip half-maximal effective concentration) of 2.40 nM.[4][5] These values were respectively 646-fold and 34-fold more potent than at the serotonin5-HT2A receptor (Ki = 373 nM,EC50 = 13.5–81.3 nM (depending on assay),EmaxTooltip maximal efficacy = 92%).[4][5] In other studies, it was apartial agonist of the serotonin 5-HT2A receptor, with anEC50 of 692 nM and anEmax of 73%.[6] In addition, it was a partial agonist of the serotonin5-HT4 receptor in the ratesophagus, with anEC50 of 355 nM and anEmax of 53%.[6] The drug has also been predicted to bind to the serotonin5-HT7 receptor, with a predicted affinity (Ki) of 631 nM.[9] In one study, relative to5-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 increasedselectivity 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 theserotonin transporter (SERT).[4][5] It showed an affinity (Ki) for the SERT of 3,006 nM and an inhibitory potency (IC50Tooltip half-maximal inhibitory concentration) in terms ofserotonin reuptake inhibition of 2,765 nM.[4] Additionally, 5-MeO-pyr-T is asubstrate of the SERT and acts as apartialserotonin releasing agent inHEK293cells, with anEC50 of 5,700 nM.[4][5]
In early literature, 5-MeO-pyr-T was described as the most potent tryptamine yet evaluated in theopen-field test, but as also having hightoxicity that would likely preclude evaluation in humans.[3][7] In subsequent modern studies, 5-MeO-pyr-T produced effects in rodents including thehead-twitch response (a behavioral proxy ofpsychedelic effects),hypothermia, andhypolocomotion.[4] Itsmedian 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]
Thechemical synthesis of 5-MeO-pyr-T has been described.[1]
Analogues of 5-MeO-pyr-T includepyr-T,4-HO-pyr-T,4-F-5-MeO-pyr-T,5-MeO-DMT, and5-MeO-DET, among others.[1] Analogues of 5-MeO-pyr-T (pyrrolidine) with differentrings, including5-MeO-pip-T (piperidine) and5-MeO-mor-T (morpholine), are also known, but have not been tested in humans.[1][6][4]
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 byAlexander Shulgin in his bookTiHKAL in 1997.[1]Robert Oberlender, from the lab ofDavid E. Nichols atPurdue University, is known to have accidentallytaken too high of a dose of 5-MeO-pyr-T and wandered outside in afugue state.[10] His experience was later included as the highest-dose 5-MeO-pyr-T experience report inTiHKAL.[10] The drug was encountered as a noveldesigner andrecreational drug inEurope by 2017.[4][11][12] 5-MeO-pyr-T'spharmacology was more fully characterized in modern studies in 2009,[6] 2023,[5] and 2024.[4]
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).
[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. [...]
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