4-F-5-MeO-pyr-T

4-F-5-MeO-pyr-T, also known as 4-fluoro-5-methoxy-N,N-pyrrolidinyltryptamine, is a serotonin 5-HT_1A receptor agonist of the tryptamine and pyrrolidinylethylindole families.^[1]^[2]^[3]^[4] It is a derivative of pyr-T and 5-MeO-DMT.^[1]^[2]^[3]

Other names4-Fluoro-5-MeO-pyr-T; 4-F,5-MeO-PyrT; 4-Fluoro-5-methoxy-N,N-pyrrolidinyltryptamine

Drug classSerotonin 5-HT_1A receptor agonist

ATC code

None

CAS Number

344790-93-8

Quick facts Clinical data, Other names ...

4-F-5-MeO-pyr-T
Clinical data


Other names	4-Fluoro-5-MeO-pyr-T; 4-F,5-MeO-PyrT; 4-Fluoro-5-methoxy-N,N-pyrrolidinyltryptamine
Drug class	Serotonin 5-HT_1A receptor agonist
ATC code	None
Identifiers
IUPAC name 4-fluoro-5-methoxy-3-(2-pyrrolidin-1-ylethyl)-1H-indole
CAS Number	344790-93-8
PubChem CID	10015574
ChemSpider	8191147
ChEMBL	ChEMBL352186
CompTox Dashboard (EPA)	DTXSID501201608
Chemical and physical data
Formula	C₁₅H₁₉FN₂O
Molar mass	262.328 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COC1=C(C2=C(C=C1)NC=C2CCN3CCCC3)F
InChI InChI=1S/C15H19FN2O/c1-19-13-5-4-12-14(15(13)16)11(10-17-12)6-9-18-7-2-3-8-18/h4-5,10,17H,2-3,6-9H2,1H3 Key:FJCRAYWNOXUYOO-UHFFFAOYSA-N

Pharmacology

4-F-5-MeO-pyr-T acts as a highly potent and selective serotonin 5-HT_1A receptor full agonist.^[1]^[2]^[3] It shows about 813-fold selectivity in activating this receptor over the related serotonin 5-HT_2A receptor.^[4] The drug shows little activity at other serotonin receptors besides the serotonin 5-HT_1A receptor and little activity at the serotonin transporter (SERT) or other monoamine transporters (MATs).^[4]

4-F-5-MeO-pyr-T does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and this is the case regardless of whether it is administered alone or in combination with the serotonin 5-HT_1A receptor antagonist WAY-100635.^[4] Likewise, 4-F-5-MeO-pyr-T does not substitute for the psychedelics DOI and LSD in animal drug discrimination tests.^[3] However, it fully substitutes for the serotonin 5-HT_1A receptor full agonist LY-293284 in such tests.^[3] 4-F-5-MeO-pyr-T produces serotonin 5-HT_1A receptor-dependent antidepressant-like effects in rodents.^[4]^[5] It also dose-dependently produces hypolocomotion in rodents.^[4] At higher doses, 4-F-5-MeO-pyr-T induces a pronounced serotonin syndrome and behavioral disruption in rodents, including flat body posture and forepaw treading.^[3]

4-F-5-MeO-pyr-T is a potential alternative to 8-OH-DPAT as a serotonin 5-HT_1A receptor agonist for use in scientific research.^[3]

History

4-F-5-MeO-pyr-T was first synthesized and described by David E. Nichols and colleagues in 2001.^[1]^[2]^[3]

References

[1]
Nichols DE (2017). "Chemistry and Structure–Activity Relationships of Psychedelics". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. The 4-fluoro compound (6) had 0.23 nM affinity at the human 5-HT1A receptor, nearly ten-fold greater than 5-MeO-DMT itself (1.7 nM). This substitution pattern was then exploited to create a 5-HT1A ligand by replacing the N,N-dimethyl substituents with a pyrrolidyl moiety to afford molecule 8, with 0.12 nM affinity at the human 5-HT1A receptor and in vivo potency in the drug discrimination assay in rats comparable to the 5-HT1A agonist 8-OH-DPAT (Laban et al. 2001).
[2]
Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X. The 4-fluoro-5-methoxy-DMT compound (3) had affinity at the human 5-HT1A receptor of 0.23 nM, a nearly 10-fold increase over 5-MeO-DMT itself (1.7 nM). This substitution pattern was later exploited to create a 5-HT1A ligand by replacing the N, N-dimethyl substituents with a pyrrolidyl moiety4 to afford a molecule 5, Figure 4, with exceptionally high 5-HT1A receptor affinity and in vivo potency in the drug discrimination assay in rats trained to discriminate the 5-HT1A agonist LY293284 from saline.7 [...]
[3]
Laban U, Kurrasch-Orbaugh D, Marona-Lewicka D, Nichols DE (March 2001). "A novel fluorinated tryptamine with highly potent serotonin 5-HT1A receptor agonist properties". Bioorganic & Medicinal Chemistry Letters. 11 (6): 793–795. doi:10.1016/s0960-894x(01)00062-2. PMID 11277522.
[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. PMC 11152992. PMID 38720072.{{cite journal}}: CS1 maint: overridden setting (link)
[5]
"Toad psychedelic points to biological target for antidepressants". Nature. May 2024. doi:10.1038/d41586-024-01296-x. PMID 38719960.

Pharmacology

History

See also

References

External links

Related Articles

Timelines

Top Qs

Fact Checks