Pyr-T

Pyr-T
Clinical data
Other namesN,N-Tetramethylenetryptamine; N,N-Pyrrolidinyltryptamine; Pyrrolidinyltryptamine; Pyr-Tryptamine; 3-(2-Pyrrolidinoethyl)indole
Routes of
administration		Oral, inhalation
Drug classSerotonin receptor modulator
ATC code
  • None
Identifiers
  • 3-[2-(pyrrolidin-1-yl)ethyl]-1H-indole
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H18N2
Molar mass214.312 g·mol−1
3D model (JSmol)
Melting point193 to 194 °C (379 to 381 °F) (hydrochloride salt)
Boiling point170 to 180 °C (338 to 356 °F) (freebase at 0.05 mm/Hg)
  • c2c(c1ccccc1[nH]2)CCN3CCCC3
  • InChI=1S/C14H18N2/c1-2-6-14-13(5-1)12(11-15-14)7-10-16-8-3-4-9-16/h1-2,5-6,11,15H,3-4,7-10H2 checkY
  • Key:CVTZCBLFHNGYDQ-UHFFFAOYSA-N checkY
  (verify)

Pyr-T, also known as N,N-tetramethylenetryptamine or as 3-(2-pyrrolidinoethyl)indole, is a lesser-known serotonin receptor modulator of the tryptamine and pyrrolidinylethylindole families. It is the cyclized derivative of diethyltryptamine (DET) in which the N,N-diethyl groups have been fused into a pyrrolidine ring.

Use and effects

In his 1997 book TiHKAL (Tryptamines I Have Known and Loved), Alexander Shulgin reported neither the dose range nor the duration of the drug. However, individual experiments employed 25 to 50 mg orally and 70 mg smoked. Pyr-T produced effects including malaise, feeling sick, unpleasantness, salivation, muscle and joint pains, dizziness, feeling high, and uncomfortableness. Hallucinogenic effects, for instance visuals, were either absent or minor.

Interactions

Pharmacology

Pharmacodynamics

Pyr-T has been found to show affinity for serotonin receptors, including the serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. Its affinities (IC50Tooltip half-maximal inhibitory concentration) for these receptors were 30 nM for the serotonin 5-HT1A receptor, 110 nM for the 5-HT2A receptor, and 750 nM for the serotonin 5-HT2B receptor. The affinities of pyr-T for the serotonin 5-HT2A and 5-HT2B receptors were similar to but slightly lower than those of dimethyltryptamine (DMT), whereas its affinity for the serotonin 5-HT1A receptor was 5.7-fold higher than that of DMT and was intermediate between those of DMT and 5-MeO-DMT. The serotonin 5-HT1A to 5-HT2A receptor affinity ratios in the study were about 0.27 for pyr-T, 0.5 for 5-MeO-DMT, 1.4 for bufotenin, 2.3 for DMT, and 32 for psilocin. Pyr-T is a serotonin receptor agonist in the rat uterus and stomach strip, with similar potency as dimethyltryptamine (DMT).

Pyr-T has been found to produce behavioral changes in animal tests. It was described as being as potent as diethyltryptamine (DET) in rodents, cats, and primates, but that it also had a poor margin of activity relative to toxicity and was unlikely to be tested in humans. It has been found to produce hypolocomotion in rodents. Conversely, pyr-T (3 mg/kg) failed to acutely produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.

Chemistry

Pyr-T is a pyrrolidinylethylindole and a substituted tryptamine in which the amine moiety has been replaced with a pyrrolidine ring. It can be thought of as a cyclized derivative of diethyltryptamine (DET) in which the N,N-ethyl groups have been connected to form the pyrrolidine ring present in pyr-T.

Synthesis

The chemical synthesis of pyr-T has been described.

Analogues

Derivatives of pyr-T include 4-HO-pyr-T, 5-MeO-pyr-T, and 4-F-5-MeO-pyr-T. Analogues of pyr-T include pip-tryptamine, 10,11-secoergoline (α,N-Pip-T), MPMI, and SN-22, among others.

History

Pyr-T was first characterized by Mitzal by 1962. Animal toxicity testing was later performed by Hunt and Brimblecombe by 1967. The effects of pyr-T in humans were described by Alexander Shulgin in his book TiHKAL in 1997.

See also

References

  1. 1 2 3 4 5 6 7 Shulgin A, Shulgin A (1997). TiHKAL, The Continuation (1st ed.). Berkeley, CA, USA: Transform Press. pp. 577–578. ISBN 978-0-9630096-9-2. Retrieved 7 April 2018.
  2. 1 2 3 4 5 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).
  3. ↑ Krasowski MD, Ekins S (2014). "Using cheminformatics to predict cross reactivity of "designer drugs" to their currently available immunoassays". Journal of Cheminformatics. 6: 22. doi:10.1186/1758-2946-6-22. PMC 4029917. PMID 24851137.
  4. 1 2 3 Nichols DE (2018). "Chemistry and Structure-Activity Relationships of Psychedelics". Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. Tethering the dialkyl groups into a heterocyclic ring gave mixed results; N-pyrrolidyl had an affinity similar to N,N-dimethyltryptamine (110 vs. 75 nM, respectively), but the affinity for the N-piperidyl was much lower, at 760 nM.
  5. 1 2 3 4 McKenna DJ, Repke DB, Lo L, Peroutka SJ (March 1990). "Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes". Neuropharmacology. 29 (3): 193–198. doi:10.1016/0028-3908(90)90001-8. PMID 2139186.
  6. ↑ Barlow RB, Khan I (March 1959). "Actions of some analogues of tryptamine on the isolated rat uterus and on the isolated rat fundus strip preparations". Br J Pharmacol Chemother. 14 (1): 99–107. doi:10.1111/j.1476-5381.1959.tb00934.x. PMC 1481812. PMID 13651585.
  7. 1 2 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 3 Abiero A, Ryu IS, Botanas CJ, Custodio RJ, Sayson LV, Kim M, et al. (January 2020). "Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice". Biomol Ther (Seoul). 28 (1): 83–91. doi:10.4062/biomolther.2019.049. PMC 6939696. PMID 31230432.
  9. ↑ Shulgin A, Shulgin A (1997). TiHKAL, The Continuation (1st ed.). Berkeley, CA, USA: Transform Press. pp. 577–578. ISBN 978-0-9630096-9-2. Retrieved 7 April 2018.
  10. ↑ Mitzal S (1962). "N/A". Dissertationes Pharm. 14: 305.