Pip-Tryptamine

{{Lowercase title}} {{Infobox drug | drug_name = pip-Tryptamine | image = Pip-Tryptamine.svg | image_class = skin-invert-image | width = 200px | image2 = pip-T 3D.png | image_class2 = bg-transparent | width2 = 225px

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| IUPAC_name = 3-(2-piperidin-1-ylethyl)-1''H''-indole | C=15 | H=20 | N=2 | SMILES = C1CCN(CC1)CCC2=CNC3=CC=CC=C32 | StdInChI = 1S/C15H20N2/c1-4-9-17(10-5-1)11-8-13-12-16-15-7-3-2-6-14(13)15/h2-3,6-7,12,16H,1,4-5,8-11H2 | StdInChIKey = PJVCNRSWJSLGCV-UHFFFAOYSA-N }}

'''pip-Tryptamine''' ('''pip-T'''), also known as '''''N'',''N''-pentamethylenetryptamine''', '''''N'',''N''-piperidyltryptamine''', or '''3-(2-piperidinoethyl)indole''', is a serotonin receptor modulator and possible serotonergic psychedelic of the tryptamine family.<ref name="Nichols2018">{{cite book | vauthors = Nichols DE | chapter = Chemistry and Structure–Activity Relationships of Psychedelics | title = Behavioral Neurobiology of Psychedelic Drugs | journal = Current Topics in Behavioral Neurosciences | series = Curr Top Behav Neurosci | volume = 36 | issue = | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | url = | quote = A systematic study of the effect of N-alkylation on tryptamine receptor affinities was reported by McKenna et al. (1990). N-alkylated tryptamines were examined with no ring substituents, a 5-methoxy, or 4-hydroxy group. Highest affinities (4–30 nM) for displacement of [125I]DOI from rat cortical homogenate were observed with N,N-dimethyl, N,N-diethyl, N-methyl-N-isopropyl, and N,N-diisopropyl substituents. An affinity of 39 nM was reported for 4-OH-N,N-di(sec-butyl) tryptamine, but the affinity of 4-OH-N,N-diisobutyltryptamine was only 260 nM. 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.}}</ref><ref name="TiHKAL">{{cite book | author1 = Alexander T. Shulgin | author2 = Ann Shulgin | chapter = #52. PYR-T TRYPTAMINE, N,N-TETRAMETHYLENE; INDOLE, 3-[2-(1-PYRROLIDYL)ETHYL]; PYRROLIDINE, 1-[2-(3-INDOLYL)ETHYL]; N,N-TETRAMETHYLENETRYPTAMINE; 1-[2-(1H-INDOL-3-YL)ETHYL]PYRROLIDINE; 1-[2-(1-PYRROLIDYL)ETHYL]INDOLE; "PYRROLIDYLTRYPTAMINE" | pages = 577–578 | chapter-url = https://erowid.org/library/books_online/tihkal/tihkal52.shtml | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-0-9 | oclc = 25627628 | url = https://books.google.com/books?id=O8AdHBGybpcC | quote = EXTENSIONS AND COMMENTARY: First of all, the name pyr-T, which is an abbreviation for “pyrrolidinyltryptamine,” is out-and-out wrong. There is just one single nitrogen at the end of the tryptamine chain and it cannot be claimed by both halves of the name. It is intrinsic to the name pyrrolidine as well as to the name tryptamine. This is why the name is in quotation marks. This drug has occasionally been called PT in the popular literature, but choosing to spell it out as pyr-T allows a parallel code to be used with the piperidine and morpholine analogues. These two analogues are both described in the literature. The piperidine material (pip-T) is made via the glyoxylamide (mp 182-183 °C) which is reduced with LAH to the target amine (mp 149-150 °C, HC1 salt 220-221 °C). The morpholine analogue (mor-T) also came to be via the glyoxylamide (mp 187-188 °C) and the reduction to the amine which can be an oil, but which has been reported to have a mp 145- 147 °C. The only trials I know of with either of these is with mor-T which, as the fumarate salt, had no effects at all upon the i.m. injection of a 30 milligram bolus. Actually, this neat trilogy of heterocyclics, the pyrrolidine ring, the piperidine ring, and the morpholine ring, have been the chemist's favorite for many years. Leaf through the “Known Tryptamines” appendix, and see how often you see stretched between the nitrogen substituents the phrases: [...]}}</ref><ref name="McKennaRepke1990">{{cite journal | vauthors = McKenna DJ, Repke DB, Lo L, Peroutka SJ | title = Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes | journal = Neuropharmacology | volume = 29 | issue = 3 | pages = 193–198 | date = March 1990 | pmid = 2139186 | doi = 10.1016/0028-3908(90)90001-8 | url = | doi-access = free }}</ref><ref name="AbieroRyuBotanas2020">{{cite journal | vauthors = Abiero A, Ryu IS, Botanas CJ, Custodio RJ, Sayson LV, Kim M, Lee HJ, Kim HJ, Seo JW, Cho MC, Lee KW, Yoo SY, Jang CG, Lee YS, Cheong JH | title = Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice | journal = Biomol Ther (Seoul) | volume = 28 | issue = 1 | pages = 83–91 | date = January 2020 | pmid = 31230432 | pmc = 6939696 | doi = 10.4062/biomolther.2019.049 | url = }}</ref><ref name="BarlowKhan1959">{{cite journal | vauthors = Barlow RB, Khan I | title = Actions of some analogues of tryptamine on the isolated rat uterus and on the isolated rat fundus strip preparations | journal = Br J Pharmacol Chemother | volume = 14 | issue = 1 | pages = 99–107 | date = March 1959 | pmid = 13651585 | pmc = 1481812 | doi = 10.1111/j.1476-5381.1959.tb00934.x | url = }}</ref><ref name="Cami-KobeciSlatfordWhittlesey2005">{{cite journal | vauthors = Cami-Kobeci G, Slatford PA, Whittlesey MK, Williams JM | title = N-Alkylation of phenethylamine and tryptamine | journal = Bioorg Med Chem Lett | volume = 15 | issue = 3 | pages = 535–537 | date = February 2005 | pmid = 15664808 | doi = 10.1016/j.bmcl.2004.11.050 | url = | quote = We were pleased to find that reaction of tryptamine (12) with the appropriate diol (16, 23 and 24) resulted in good conversion to the corresponding pyrrolidine 25, and piperidine 26, and in reasonable isolated yield into azepane 27 (Scheme 6).}}</ref> It is the derivative of tryptamine in which the amine has been cyclized into a piperidine ring.<ref name="Nichols2018" /><ref name="TiHKAL" /><ref name="McKennaRepke1990" />

==Use and effects== pip-T was only briefly mentioned by Alexander Shulgin in his book ''TiHKAL'' (''Tryptamines I Have Known and Loved'').<ref name="TiHKAL" /> Its properties and effects were not described.<ref name="TiHKAL" />

==Interactions== {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology== ===Pharmacodynamics=== The affinities ({{Abbrlink|IC50|half-maximal inhibitory concentration}}) of pip-tryptamine for serotonin receptors were 600{{nbsp}}nM for the serotonin 5-HT1A receptor, 760{{nbsp}}nM for the serotonin 5-HT2A receptor, and 1,250{{nbsp}}nM for the serotonin 5-HT2B receptor, whereas other serotonin receptors were not reported.<ref name="Nichols2018" /><ref name="McKennaRepke1990" /> The affinity of pip-T for the serotonin 5-HT2A receptor was about 10-fold lower than that of dimethyltryptamine (DMT) and was about 7-fold lower than that of pyr-tryptamine (pyr-T; ''N'',''N''-pyrrolidinyltryptamine).<ref name="McKennaRepke1990" /> Pip-T is a serotonin receptor agonist in the rat uterus with similar potency as DMT, but showed 20-fold lower potency than DMT in the rat fundus strip.<ref name="BarlowKhan1959">{{cite journal | vauthors = Barlow RB, Khan I | title = Actions of some analogues of tryptamine on the isolated rat uterus and on the isolated rat fundus strip preparations | journal = Br J Pharmacol Chemother | volume = 14 | issue = 1 | pages = 99–107 | date = March 1959 | pmid = 13651585 | pmc = 1481812 | doi = 10.1111/j.1476-5381.1959.tb00934.x | url = }}</ref>

The drug produces hypolocomotion in rodents.<ref name="AbieroRyuBotanas2020" /> In addition, it induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.<ref name="AbieroRyuBotanas2020" /> This was blocked by the serotonin 5-HT2A receptor antagonist ketanserin.<ref name="AbieroRyuBotanas2020" /> Hence, the drug may have hallucinogenic effects in humans.<ref name="AbieroRyuBotanas2020" /> Conversely, pip-T did not produce conditioned place preference (CPP) and was not self-administered, suggesting that it lacks reinforcing properties and misuse potential, similarly to most other tryptamines.<ref name="AbieroRyuBotanas2020" />

==Chemistry== ===Synthesis=== The chemical synthesis of pip-T has been described.<ref name="TiHKAL" />

===Analogues=== Analogues of pip-T include 5-MeO-pip-T, 10,11-secoergoline (α,''N''-Pip-T), pyr-T, MPMI, SN-22, RU-24,969, and EMD-386088, among others.

====mor-Tryptamine==== thumb|left|150px|class=skin-invert-image|mor-Tryptamine structure.

mor-Tryptamine, or mor-T, also known as 3-(2-morpholinoethyl)indole, is the analogue of pip-T with the piperidine ring replaced with a morpholine ring.<ref name="TiHKAL" /> It was briefly described by Alexander Shulgin in his book ''TiHKAL'' (''Tryptamines I Have Known and Loved''), including its chemical synthesis.<ref name="TiHKAL" /> The drug was tested by intramuscular injection of 30{{nbsp}}mg as the fumarate salt, but produced no effects whatsoever.<ref name="TiHKAL" /> Accordingly, mor-T was completely inactive as a serotonin receptor agonist in the rat uterus and rat stomach strip.<ref name="BarlowKhan1959" /> The 5-methoxy derivative of mor-T, 5-MeO-mor-T, is also known, but is not known to have been tested.<ref name="TiHKAL" />

==History== Pip-T was first described in the scientific literature by 1959<ref name="BarlowKhan1959" /> and was more thoroughly characterized in 1990<ref name="Nichols2018" /><ref name="McKennaRepke1990" /> and 2020.<ref name="AbieroRyuBotanas2020" />

==See also== * Substituted tryptamine * Cyclized tryptamine

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5189 pip-T - Isomer Design]

Category:N,N-Dialkyltryptamines Category:Piperidines Category:Psychedelic tryptamines Category:Serotonin receptor modulators