Chemistry:4-Fluoro-DMT

From HandWiki

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]

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) and efficacies (Emax) 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 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. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Synthesis and pharmacological evaluation of fluorinated hallucinogenic tryptamine analogs and thienopyrrole bioisosteres of N,N-dimethyltryptamine". August 1997. https://docs.lib.purdue.edu/dissertations/AAI9818919/. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist". Bioorganic & Medicinal Chemistry Letters 15 (20): 4555–4559. October 2005. doi:10.1016/j.bmcl.2005.06.104. PMID 16061378. 
  3. ↑ 3.0 3.1 "4-Fluoroindole and Derivatives". Israel Journal of Chemistry 2 (1): 25–28. 1964. doi:10.1002/ijch.196400006. ISSN 0021-2148. 
  4. ↑ "Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines". Journal of Medicinal Chemistry 43 (24): 4701–4710. November 2000. doi:10.1021/jm000339w. PMID 11101361. 

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:4-Fluoro-DMT&oldid=3739317"