4-F-5-MeO-pyr-T does not produce thehead-twitch response, a behavioral proxy ofpsychedelic effects, in rodents, and this is the case regardless of whether it is administered alone or in combination with the serotonin 5-HT1A receptorantagonistWAY-100635.[4] Likewise, 4-F-5-MeO-pyr-T does not substitute for the psychedelicsDOI andLSD in animaldrug discrimination tests.[3] However, it fully substitutes for the serotonin 5-HT1A receptorfull agonistLY-293284 in such tests.[3] 4-F-5-MeO-pyr-T produces serotonin 5-HT1A receptor-dependentantidepressant-like effects in rodents.[4][5] It alsodose-dependently produceshypolocomotion in rodents.[4] At higher doses, 4-F-5-MeO-pyr-T induces a pronouncedserotonin syndrome and behavioral disruption in rodents, including flat body posture and forepaw treading.[3]
4-F-5-MeO-pyr-T is a potential alternative to8-OH-DPAT as a serotonin 5-HT1A receptor agonist for use inscientific research.[3]
^abcdNichols 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.ISBN978-3-662-55878-2.PMID28401524.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).
^abcdNichols 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.ISSN2190-460X.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 [...]
^abcdefghLaban 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.PMID11277522.
