Difluoromescaline

Difluoromescaline
Clinical data
Other names	DFM; 4-Difluoromethoxy-3,5-dimethoxyphenethylamine; 3,5-Dimethoxy-4-difluoromethoxyphenethylamine
Routes of; administration	Oral
Drug class	Serotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code	None;
Pharmacokinetic data
Duration of action	12–18 hours
Identifiers
	IUPAC name 2-[4-(difluoromethoxy)-3,5-dimethoxyphenyl]ethanamine;
CAS Number	1178367-63-9;
PubChem CID	54930734;
ChemSpider	33250437;
Chemical and physical data
Formula	C11H15F2NO3
Molar mass	247.242 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC1=CC(=CC(=C1OC(F)F)OC)CCN;
	InChI InChI=1S/C11H15F2NO3/c1-15-8-5-7(3-4-14)6-9(16-2)10(8)17-11(12)13/h5-6,11H,3-4,14H2,1-2H3; Key:MMARNDCKXDBJES-UHFFFAOYSA-N;

Difluoromescaline (DFM), also known as 4-difluoromethoxy-3,5-dimethoxyphenethylamine, is a psychedelic drug of the phenethylamine and scaline families related to mescaline.^[1]^[2]^[3] It is a difluorinated derivative of mescaline.^[1]^[2]^[3] The drug's dose range is 50 to 100 mg orally and its duration is 12 to 18 hours.^[1]^[2]^[3] It is about 3- or 4-fold more potent than mescaline and has a longer duration in comparison.^[1]^[2] The drug is said to produce strong psychedelic effects.^[3] Difluoromescaline interacts with serotonin receptors and acts as a low-potency full agonist of the serotonin 5-HT_2A receptor.^[1]^[2]^[3] It was first described in the scientific literature by Daniel Trachsel in 2012.^[2]^[1]^[3] The drug's pharmacology was studied in more detail in 2021.^[3]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine Von der Struktur zur Funktion. Nachtschatten Verlag AG. pp. 705, 708–710, 716–718, 723, 736–737. ISBN 978-3-03788-700-4.
^ ^a ^b ^c ^d ^e ^f ^g ^h Trachsel D (2012). "Fluorine in psychedelic phenethylamines". Drug Testing and Analysis. 4 (7–8): 577–590. doi:10.1002/dta.413. PMID 22374819. Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human potency and duration of mescaline (22) effects. [...] Among numerous modifications of the 4-position,[3,86] 4-fluoroalkoxy derivatives have been prepared and investigated (Figure 5).[86] The smallest investigated fluoro analogs of mescaline (22: 180–360 mg, 10–12 h), namely difluoromescaline (72: 50–100 mg, 12–18 h) and trifluoromescaline (73: 15–40 mg, 14– 24 h) proved to show psychedelic properties, with 73 being one of the most potent mescaline derivatives so far discovered. At least for 72 (Ki= 5949nM) the affinity at the antagonistic [3 H]ketanserinlabelled serotonin h5-HT2A receptor was determined, which was not significantly different from mescaline (22. Ki= 5500nM[85]). As observed with escaline (70),[85] affinity alone cannot explain increased in vivo activity. The long lasting effects of 72 and 73 could also result from enhanced metabolic stabilities as a consequence of fluorination. [...] A total number of 14 fluorinated mescaline analogs/homologs have been described (72, 73, 75–78, 80–82, 84, 86–89; 3,4,5-series). The simplest analogs, difluoromescaline (72: 50–100 mg, 12–18 h) as well as trifluoromescaline (73: 15–40 mg, 14–24 h) have proven to be more potent and showed distinctly longer duration of action in humans when compared to mescaline (22: 180–360 mg, 10–12 h).
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME (2021). "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Frontiers in Pharmacology. 12 794254. doi:10.3389/fphar.2021.794254. PMC 8865417. PMID 35222010. Introduction of fluorinated alkyloxy groups onto the 4-position of mescaline (5) has also led to derivatives with increased human potency when compared to 5 (Figure 2). These derivatives include difluoromescaline (DFM; 12) and trifluromescaline (TFM; 13), which have a 4-fold and > 9-fold increase in human potency, respectively. Both substances induce strong psychedelic effects and have significantly longer lasting effects than mescaline, with 13 being among the most potent mescaline-based derivatives synthesized to date (Trachsel 2012).

External links

Difluoromescaline - Isomer Design

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[Trachsel_2013-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine Von der Struktur zur Funktion. Nachtschatten Verlag AG. pp. 705, 708–710, 716–718, 723, 736–737. ISBN 978-3-03788-700-4.

[Trachsel_2012-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h Trachsel D (2012). "Fluorine in psychedelic phenethylamines". Drug Testing and Analysis. 4 (7–8): 577–590. doi:10.1002/dta.413. PMID 22374819. Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human potency and duration of mescaline (22) effects. [...] Among numerous modifications of the 4-position,[3,86] 4-fluoroalkoxy derivatives have been prepared and investigated (Figure 5).[86] The smallest investigated fluoro analogs of mescaline (22: 180–360 mg, 10–12 h), namely difluoromescaline (72: 50–100 mg, 12–18 h) and trifluoromescaline (73: 15–40 mg, 14– 24 h) proved to show psychedelic properties, with 73 being one of the most potent mescaline derivatives so far discovered. At least for 72 (Ki= 5949nM) the affinity at the antagonistic [3 H]ketanserinlabelled serotonin h5-HT2A receptor was determined, which was not significantly different from mescaline (22. Ki= 5500nM[85]). As observed with escaline (70),[85] affinity alone cannot explain increased in vivo activity. The long lasting effects of 72 and 73 could also result from enhanced metabolic stabilities as a consequence of fluorination. [...] A total number of 14 fluorinated mescaline analogs/homologs have been described (72, 73, 75–78, 80–82, 84, 86–89; 3,4,5-series). The simplest analogs, difluoromescaline (72: 50–100 mg, 12–18 h) as well as trifluoromescaline (73: 15–40 mg, 14–24 h) have proven to be more potent and showed distinctly longer duration of action in humans when compared to mescaline (22: 180–360 mg, 10–12 h).

[Kolaczynska_2021-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME (2021). "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Frontiers in Pharmacology. 12 794254. doi:10.3389/fphar.2021.794254. PMC 8865417. PMID 35222010. Introduction of fluorinated alkyloxy groups onto the 4-position of mescaline (5) has also led to derivatives with increased human potency when compared to 5 (Figure 2). These derivatives include difluoromescaline (DFM; 12) and trifluromescaline (TFM; 13), which have a 4-fold and > 9-fold increase in human potency, respectively. Both substances induce strong psychedelic effects and have significantly longer lasting effects than mescaline, with 13 being among the most potent mescaline-based derivatives synthesized to date (Trachsel 2012).

[1]

[2]

[3]

See also

References

External links