4-Fluoro-DMT

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4-Fluoro-DMT
4-Fluoro-dimethyltryptamine.svg
Clinical data
Other names4-Fluoro-N,N-dimethyltryptamine; 4-F-DMT; 4F-DMT
Drug class Serotonin 5-HT2C receptor agonist
Identifiers
  • 2-(4-fluoro-1H-indol-3-yl)-N,N-dimethylethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C12H15FN2
Molar mass 206.264 g·mol−1
3D model (JSmol)
  • CN(C)CCC1=CNC2=C1C(=CC=C2)F
  • InChI=1S/C12H15FN2/c1-15(2)7-6-9-8-14-11-5-3-4-10(13)12(9)11/h3-5,8,14H,6-7H2,1-2H3
  • Key:ISJZKVWGUWBUFG-UHFFFAOYSA-N

4-Fluoro-DMT (or 4-F-DMT), also known as 4-fluoro-N,N-dimethyltryptamine, is a serotonin receptor agonist of the tryptamine family and a close analogue of psilocin (4-HO-DMT) and dimethyltryptamine (DMT). [1] [2] [3] It is a modestly selective serotonin 5-HT2C receptor full agonist and doesn't appear to produce psychedelic-like effects in animals but instead produces antiobsessional-like effects. [1] [2]

Contents

Pharmacology

The drug's affinity (Ki) for the serotonin 5-HT1A receptor was 135 nM. [1] This can be compared to psilocin's affinity of 378 nM and serotonin's affinity of 1.7 nM. [1] In another study, 4-F-DMT showed affinities (Ki) of 335 nM for the serotonin 5-HT2A receptor, 8.39 nM for the serotonin 5-HT2B receptor, and 82–84 nM for the serotonin 5-HT2C receptor. [2] Its activational potencies (EC50 Tooltip half-maximal effective concentration) and efficacies (Emax Tooltip maximal efficacy) were 949 nM (49%) at the serotonin 5-HT2A receptor, 1,180 nM (38%) at the serotonin 5-HT2B receptor, and 99 nM (93%) at the serotonin 5-HT2C receptor. [2] 4-F-DMT showed dramatically less potent EC50 values at the serotonin 5-HT2A and 5-HT2B receptors compared to psilocin (40- and 20-fold less potent), whereas its potency was less markedly reduced at the serotonin 5-HT2C receptor (about 3-fold less potent). [2] Hence, whereas psilocin is a balanced agonist of the serotonin 5-HT2 receptors, 4-F-DMT is a selective serotonin 5-HT2C receptor agonist with about 10-fold preference for activation of this receptor over the serotonin 5-HT2A and 5-HT2B receptors. [2] Moreover, whereas psilocin was a partial agonist of the serotonin 5-HT2C receptor (Emax = 51%), 4-F-DMT had higher efficacy and was a full agonist (Emax = 93%). [2]

4-F-DMT produced partial generalization (0–56%) to LSD in animal drug discrimination tests, but this was not statistically significant and an ED50 Tooltip median effective dose was not calculated. [1] It also failed to substitute for DOI in drug discrimination tests (10–33%). [1] Conversely, psilocin produced full generalization at much lower doses. [1] Hence, 4-F-DMT may not be hallucinogenic in humans. [1] On the other hand, the drug was dose-dependently and strongly active in producing antiobsessional-like effects in an animal model of obsessive–compulsive disorder (OCD) (specifically inhibition of serotonin-induced scratching behavior), an effect that it is thought may be mediated by serotonin 5-HT2C receptor agonism. [2]

Chemistry

4-F-DMT is more lipophilic than psilocin (4-HO-DMT) due to lacking its hydrophilic hydroxyl group, and hence 4-F-DMT might cross the blood–brain barrier more readily than psilocin. [2]

Derivatives of 4-F-DMT such as 4-fluoro-5-methoxy-DMT (4-F-5-MeO-DMT) have also been synthesized and studied. [4]

History

4-F-DMT was first synthesized and described in the scientific literature by 1964. [3]

See also

References

  1. 1 2 3 4 5 6 7 8 Blair JB (August 1997). "Synthesis and pharmacological evaluation of fluorinated hallucinogenic tryptamine analogs and thienopyrrole bioisosteres of N,N-dimethyltryptamine". Purdue e-Pubs. Retrieved 20 March 2025.
  2. 1 2 3 4 5 6 7 8 9 Sard H, Kumaran G, Morency C, Roth BL, Toth BA, He P, et al. (October 2005). "SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist". Bioorganic & Medicinal Chemistry Letters. 15 (20): 4555–4559. doi:10.1016/j.bmcl.2005.06.104. PMID   16061378.
  3. 1 2 Bentov M, Pelchowicz Z, Levy A (1964). "4-Fluoroindole and Derivatives". Israel Journal of Chemistry. 2 (1): 25–28. doi:10.1002/ijch.196400006. ISSN   0021-2148.
  4. ↑ Blair JB, Kurrasch-Orbaugh D, Marona-Lewicka D, Cumbay MG, Watts VJ, Barker EL, et al. (November 2000). "Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines". Journal of Medicinal Chemistry. 43 (24): 4701–4710. doi:10.1021/jm000339w. PMID   11101361.
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