5-MeO-pyr-T
5-MeO-pyr-T, also known as 5-methoxy-N,''N-tetramethylenetryptamine or as 5-methoxy-3-indole, is a serotonin receptor modulator and psychedelic drug of the tryptamine, 5-methoxytryptamine, and pyrrolidinylethylindole families. 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.
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. 5-MeO-pyr-T shows far greater selectivity for the serotonin 5-HT1A receptor than 5-MeO-DMT.
5-MeO-pyr-T was first described in the scientific literature by 1962.
Use and effects
In his book TiHKAL, Alexander Shulgin gives the dose of 5-MeO-pyr-T as 0.5 to 2mg orally and its duration as "several hours". It was also assessed at doses of 1 to 4mg smoked.The drug's effects were dose-dependent and variably included intense tinnitus, nausea and vomiting, miosis, confusion or cognitive impairment, uncomfortableness, minor dysphoria, partial to complete amnesia, flailing, rolling about, quivering, and shaking, unconsciousness, and prolonged hangover. 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 or the clarity or 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". 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". Its effects have also been described as "white-out" analogously to 5-MeO-DMT and with amplified amnesic effects compared to 5-MeO-DMT.
The effects of 5-MeO-pyr-T appear to be highly variable between individuals. 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. Shulgin has also described 5-MeO-pyr-T as being "not hallucinogenic" and instead as producing "long-lived amnesia and unconsciousness".
Pharmacology
Pharmacodynamics
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. At the serotonin 5-HT1A receptor, it had an affinity of 0.577nM and an activational potency of 2.40nM. These values were respectively 646-fold and 34-fold more potent than at the serotonin 5-HT2A receptor. In other studies, it was a partial agonist of the serotonin 5-HT2A receptor, with an of 692nM and an of 73%. In addition, it was a partial agonist of the serotonin 5-HT4 receptor in the rat esophagus, with an of 355nM and an of 53%. The drug has also been predicted to bind to the serotonin 5-HT7 receptor, with a predicted affinity of 631nM. 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.Besides the serotonin receptors, 5-MeO-pyr-T is very weakly active at the serotonin transporter. It showed an affinity for the SERT of 3,006nM and an inhibitory potency in terms of serotonin reuptake inhibition of 2,765nM. Additionally, 5-MeO-pyr-T is a substrate of the SERT and acts as a partial serotonin releasing agent in HEK293 cells, with an of 5,700nM.
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. In subsequent modern studies, 5-MeO-pyr-T produced effects in rodents including the head-twitch response, hypothermia, and hypolocomotion. Its median effective dose for producing the head-twitch response was slightly higher than that of 5-MeO-DMT, whereas it was much less efficacious in inducing the response compared to 5-MeO-DMT and produced only a weak maximal effect. 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.