5-MeO-pip-T

Pharmaceutical compound From Wikipedia, the free encyclopedia

5-MeO-pip-T, also known as 5-methoxy-pip-tryptamine, is a serotonin receptor modulator and selective serotonin 5-HT_1A receptor agonist of the tryptamine family related to 5-MeO-pyr-T.^[1]^[2]

Other names5-Methoxy-pip-tryptamine

Drug classSerotonin receptor modulator; Selective serotonin 5-HT_1A receptor agonist

ATC code

None

PubChem CID

10467710

Quick facts Clinical data, Other names ...

5-MeO-pip-T
Clinical data


Other names	5-Methoxy-pip-tryptamine
Drug class	Serotonin receptor modulator; Selective serotonin 5-HT_1A receptor agonist
ATC code	None
Identifiers
IUPAC name 5-methoxy-3-(2-piperidin-1-ylethyl)-1H-indole
PubChem CID	10467710
ChemSpider	8643121
ChEMBL	ChEMBL292921
Chemical and physical data
Formula	C₁₆H₂₂N₂O
Molar mass	258.365 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COC1=CC2=C(C=C1)NC=C2CCN3CCCCC3
InChI InChI=1S/C16H22N2O/c1-19-14-5-6-16-15(11-14)13(12-17-16)7-10-18-8-3-2-4-9-18/h5-6,11-12,17H,2-4,7-10H2,1H3 Key:QVWFRPYLSDUCFB-UHFFFAOYSA-N

Use and effects

5-MeO-pip-T was described and partially synthesized by Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved), but he did not test it or define its properties or effects.^[1] According to Shulgin, he was not in a hurry to test it owing to the unfavorable effects of the structurally related 5-MeO-pyr-T.^[1]

Pharmacology

Pharmacodynamics

5-MeO-pip-T shows affinity for the serotonin 5-HT_2A receptor (K_i = 160–230 nM) but not for the serotonin 5-HT_2C receptor (K_i = >10,000 nM).^[2] It has been found to act as a low-potency and low-efficacy agonist of the serotonin 5-HT_2A receptor (EC₅₀Tooltip half-maximal effective concentration = 7,410 nM; E_maxTooltip maximal efficacy = 16%) and the serotonin 5-HT₄ receptor (EC₅₀ = 1,200 nM; E_maxTooltip maximal efficacy = 34%).^[3] These findings were also replicated in a subsequent study, where 5-MeO-pip-T showed far lower potency and efficacy as a serotonin 5-HT_2A receptor agonist than 5-MeO-DMT or 5-MeO-pyr-T.^[4] On the other hand, 5-MeO-pip-T was a potent full agonist of the serotonin 5-HT_1A receptor, with an EC₅₀ of 88.5 nM, although it was 42-fold less potent in this action than the highly potent 5-MeO-pyr-T.^[4] As such, 5-MeO-pip-T was described as a selective serotonin 5-HT_1A receptor agonist.^[4]

Chemistry

Synthesis

The chemical synthesis of 5-MeO-pip-T has been described.^[2]^[3]^[1]

Analogues

Analogues of 5-MeO-pip-T include pip-tryptamine (pip-T), pyr-tryptamine (pyr-T), 5-MeO-pyr-T, 5-MeO-DMT, and 5-MeO-DET, among others.^[1]

5-MeO-mor-T

5-MeO-mor-T, the 5-methoxy derivative of mor-tryptamine (mor-T) and the analogue of 5-MeO-pip-T in which the piperidine ring is replaced by a morpholine ring, was also partially synthesized and briefly described by Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved), but he did not test it.^[1]

History

5-MeO-pip-T was first described in the scientific literature by Richard Glennon and colleagues by 1994.^[2] It was briefly described by Alexander Shulgin in his 1997 book TiHKAL (Tryptamines I Have Known and Loved).^[1] The pharmacology of 5-MeO-pip-T was described in greater detail in 2024.^[4]

References

[1]
Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. "With both pyr-T and 4-HO-pyr-T, there are two additional ring analogies that are natural companions to 5-MeO-pyr-T. These are the piperidine and the morpholine counterparts, 5-MeO-mor-T and 5-MeO-pip-T. Both compounds are in the literature, and an entry reference to them can be gotten from the “known tryptamines” appendix. [...] With the rather unexpected, and unencouraging descriptions of the pyrrolidine tryptamines in general, and this one in particular, I was not too blinding a hurry to explore the two heterocyclic analogues. The amides are still on the shelf in the lab. If some good reason comes forth to assay the final amines, they can be made with a dash of lithium aluminum hydride, but until then I have other things to do."
[2]
Glennon RA, Dukat M, el-Bermawy M, Law H, De los Angeles J, Teitler M, et al. (June 1994). "Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines". Journal of Medicinal Chemistry. 37 (13): 1929–1935. doi:10.1021/jm00039a004. PMID 8027974.
[3]
Prainer BC (2009). Tryptamin-Derivate als 5-HT4-Rezeptorliganden: Synthese und in-vitro-Pharmakologie [Tryptamine derivatives as 5-HT4 receptor ligands: synthesis and in vitro pharmacology] (Thesis). pp. 42, 64, 74, 105, 156–157, 160, 162–163. doi:10.5283/EPUB.12132. Retrieved 15 June 2025.
[4]
Warren AL, Lankri D, Cunningham MJ, Serrano IC, Parise LF, Kruegel AC, et al. (June 2024). "Structural pharmacology and therapeutic potential of 5-methoxytryptamines". Nature. 630 (8015): 237–246. Bibcode:2024Natur.630..237W. doi:10.1038/s41586-024-07403-2. PMID 38720072. Extension of the methyl groups of 5-MeO-DMT (Gi BRET half-maximum effective concentration (EC50) = 25.6 nM) to one ethyl group (5-MeO-MET; Gi BRET EC50 = 25.9 nM) or two ethyl groups (5-MeO-DET; Gi BRET EC50 = 37.1 nM) only marginally affected 5-HT1A potency while retaining full efficacy, with similarly small effects at 5-HT2A (Supplementary Table 1). By contrast, a cyclic pyrrolidine substituent increased potency at 5-HT1A by about 12-fold (5-MeO-PyrT; Gi BRET EC50 = 2.1 nM) and decreased 5-HT2A potency by about 3-fold relative to 5-MeO-DMT. Cyclization of the amine moiety alone resulted in an approximately 38-fold increase in 5-HT1A > 5-HT2A selectivity. Next, we modestly decreased the steric demand of the pyrrolidine by removing two C-H bonds and installing a π bond. This change led to a further increase of around eightfold in potency at 5-HT1A (5-MeO-3-PyrrolineT; Gi BRET EC50 = 0.3 nM). By contrast, increasing the ring size to a six-membered piperidine (5-MeO-PipT; Gi BRET EC50 = 88.5 nM) led to an approximate 42-fold loss of potency relative to 5-MeO-PyrT, which indicated a sensitivity to steric bulk at 5-HT1A (Fig. 2b). [...]