Pyr-T

Pharmaceutical compound From Wikipedia, the free encyclopedia

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.^[1]^[2] It is the cyclized derivative of diethyltryptamine (DET) in which the N,N-diethyl groups have been fused into a pyrrolidine ring.^[2]

Other namesN,N-Tetramethylenetryptamine; N,N-Pyrrolidinyltryptamine; Pyrrolidinyltryptamine; Pyr-Tryptamine; 3-(2-Pyrrolidinoethyl)indole

Routes of
administrationOral, inhalation^[1]

Drug classSerotonin receptor modulator

ATC code

None

Quick facts Clinical data, Other names ...

Pyr-T
Clinical data


Other names	N,N-Tetramethylenetryptamine; N,N-Pyrrolidinyltryptamine; Pyrrolidinyltryptamine; Pyr-Tryptamine; 3-(2-Pyrrolidinoethyl)indole
Routes of administration	Oral, inhalation^[1]
Drug class	Serotonin receptor modulator
ATC code	None
Identifiers
IUPAC name 3-[2-(pyrrolidin-1-yl)ethyl]-1H-indole
CAS Number	14008-96-9^Y
PubChem CID	26393
ChemSpider	24588^Y
UNII	VZ689W7HWX
CompTox Dashboard (EPA)	DTXSID00161226
Chemical and physical data
Formula	C₁₄H₁₈N₂
Molar mass	214.312 g·mol⁻¹
3D model (JSmol)	Interactive image
Melting point	193 to 194 °C (379 to 381 °F) (hydrochloride salt)
Boiling point	170 to 180 °C (338 to 356 °F) (freebase at 0.05 mm/Hg)
SMILES c2c(c1ccccc1[nH]2)CCN3CCCC3
InChI 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^Y Key:CVTZCBLFHNGYDQ-UHFFFAOYSA-N^Y
(verify)

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.^[1]^[3] However, individual experiments employed 25 to 50 mg orally and 70 mg smoked.^[1] Pyr-T produced effects including malaise, feeling sick, unpleasantness, salivation, muscle and joint pains, dizziness, feeling high, and uncomfortableness.^[1] Hallucinogenic effects, for instance visuals, were either absent or minor.^[1]

Interactions

Pharmacology

Pharmacodynamics

Pyr-T has been found to show affinity for serotonin receptors, including the serotonin 5-HT_1A, 5-HT_2A and 5-HT_2C receptors.^[4]^[5] Its affinities (IC₅₀Tooltip half-maximal inhibitory concentration) for these receptors were 30 nM for the serotonin 5-HT_1A receptor, 110 nM for the 5-HT_2A receptor, and 750 nM for the serotonin 5-HT_2B receptor.^[4]^[5] The affinities of pyr-T for the serotonin 5-HT_2A and 5-HT_2B receptors were similar to but slightly lower than those of dimethyltryptamine (DMT), whereas its affinity for the serotonin 5-HT_1A receptor was 5.7-fold higher than that of DMT and was intermediate between those of DMT and 5-MeO-DMT.^[4]^[5] The serotonin 5-HT_1A to 5-HT_2A 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.^[5]

Pyr-T has been found to produce behavioral changes in animal tests.^[2]^[6]^[7] 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.^[2] It has been found to produce hypolocomotion in rodents.^[7] Conversely, pyr-T (3 mg/kg) failed to acutely produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.^[7]

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.^[8]

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.^[9] Animal toxicity testing was later performed by Hunt and Brimblecombe by 1967.^[2]^[6] The effects of pyr-T in humans were described by Alexander Shulgin in his book TiHKAL in 1997.^[1]

References

[1]
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]
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]
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]
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]
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.
[7]
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.
[8]
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.
[9]
Mitzal S (1962). "N/A". Dissertationes Pharm. 14: 305.