Chemistry:DOH-FLY

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DOH-FLY, also known simply as FLY or H-FLY, is a serotonin receptor agonist of the phenethylamine, DOx, and FLY families.[1][2][3][4] It is the "FLY" (benzodidihydrofuran) analogue of 2,5-dimethoxyamphetamine (2,5-DMA or DOH).[1][4]

Pharmacology

The enantiomers of FLY, (R)-FLY and (S)-FLY, show affinity and activity at the serotonin 5-HT2 receptors.[1][4] At the serotonin 5-HT2A receptor, the affinity (Ki) of (R)-FLY was 54.4 nM and of (S)-FLY was 227 nM, while at the serotonin 5-HT2C receptor, the affinity (Ki) of (R)-FLY was 8.2 nM and of (S)-FLY was 119 nM.[4] In terms of activational potency at the serotonin 5-HT2A receptor, the EC50 (Emax) of (R)-FLY was 5,650 nM (99%) while that of (S)-FLY was 2,360 nM (62%).[4] The enantiomers of FLY have greater activity as serotonin 5-HT2A receptor agonists than (R)-2,5-DMA but show dramatically lower potency than 4-substituted FLY analogues like DOB-FLY.[4] In other studies, the affinity (Ki) of racemic FLY for the serotonin 5-HT2A receptor was 2,010 nM, relative to 15 to 18 nM for DOB-FLY, 0.23 nM for Bromo-DragonFLY, and 5,200 nM for 2,5-DMA.[3][5]

FLY was included and described as an entry in Alexander Shulgin's 2011 book The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds.[1] It partially substituted for LSD in rodent drug discrimination tests, with a maximal substitution of 64% at a dose of 4.0 mmol/kg.[3] The drug was markedly less potent in these tests than 4-substituted analogues like DOB-FLY.[3] The pharmacokinetics of FLY in rats have been studied.[6] FLY is not known to have been assessed in humans, and hence it is unknown whether FLY has psychedelic or other psychoactive effects in humans.[1]

History

FLY was first described in the scientific literature by 1995.[1][3][7] It was not an explicitly controlled substance in the United States as of 2011.[1]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "#68. FLY". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 1. Berkeley, CA: Transform Press. 2011. pp. 141–143. ISBN 978-0-9630096-3-0. OCLC 709667010. https://archive.org/details/shulgin-index-vol-1/page/141/mode/1up. 
  2. ↑ (in de) Phenethylamine: von der Struktur zur Funktion. Nachtschatten-Science (1st ed.). Solothurn: Nachtschatten-Verlag. 2013. pp. 497–499, 515, 928–929. ISBN 978-3-03788-700-4. OCLC 858805226. https://books.google.com/books?id=-Us1kgEACAAJ. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Dihydrobenzofuran analogues of hallucinogens. 3. Models of 4-substituted (2,5-dimethoxyphenyl)alkylamine derivatives with rigidified methoxy groups". Journal of Medicinal Chemistry 39 (15): 2953–2961. July 1996. doi:10.1021/jm960199j. PMID 8709129. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=be8b98f51cdae9258536c6efa357b80bb22d64f1. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists". Journal of Medicinal Chemistry 44 (6): 1003–1010. March 2001. doi:10.1021/jm000491y. PMID 11300881. 
  5. ↑ "The role of lipophilicity in determining binding affinity and functional activity for 5-HT2A receptor ligands". Bioorganic & Medicinal Chemistry 16 (8): 4661–4669. April 2008. doi:10.1016/j.bmc.2008.02.033. PMID 18296055. 
  6. ↑ "LC-MS/MS analysis of two new designer drugs (FLY serie) in rat plasma and its application to a pharmacokinetic study". Legal Medicine (Tokyo, Japan) 38: 58–63. May 2019. doi:10.1016/j.legalmed.2019.04.004. PMID 30991226. 
  7. ↑ "Structure-activity relationships of hallucinogens: Design, synthesis, and pharmacological evaluation of a series of conformationally restricted phenethylamines". 1995. https://docs.lib.purdue.edu/dissertations/AAI9601547/. 




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