3-Fluorophenmetrazine

3-Fluorophenmetrazine (also known as 3-FPM, 3-FPH and PAL-593) is a phenylmorpholine-based stimulant and fluorinated analogue of phenmetrazine that has been sold online as a designer drug.[1][2]

3-Fluorophenmetrazine
Clinical data
Other names3-FPM, 3-FPH, PAL-593
Legal status
Legal status
  • CA: Unscheduled
  • DE: NpSG (Industrial and scientific use only)
  • UK: Under Psychoactive Substances Act
  • US: Unscheduled;
    Not controlled at the federal level, Schedule I in the state of Virginia
  • Illegal in Sweden and Switzerland
Identifiers
IUPAC name
  • 2-(3-Fluorophenyl)-3-methylmorpholine
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC11H14FNO
Molar mass195.237 g·mol−1
3D model (JSmol)
Boiling point280.6 °C (537.1 °F)
SMILES
  • CC1C(OCCN1)C2=CC(=CC=C2)F

  • HCl: CC1C(OCCN1)C2=CC(=CC=C2)F.Cl
InChI
  • InChI=1S/C11H14FNO/c1-8-11(14-6-5-13-8)9-3-2-4-10(12)7-9/h2-4,7-8,11,13H,5-6H2,1H3
  • Key:VHYVKJAQSJCYCK-UHFFFAOYSA-N

  • HCl: InChI=1S/C11H14FNO.ClH/c1-8-11(14-6-5-13-8)9-3-2-4-10(12)7-9;/h2-4,7-8,11,13H,5-6H2,1H3;1H
  • Key:MHJBXKFJWSBWRE-UHFFFAOYSA-N

Chemistry

3-Fluorophenmetrazine is a fluorinated analogue of phenmetrazine, a stimulant of the morpholine class.

3-Fluorophenmetrazine is a regioisomer of both 2-fluorophenmetrazine and 4-fluorophenmetrazine.

Pharmacology

3-FPM acts as a norepinephrine–dopamine releasing agent with EC50 values of 30 nM and 43 nM, respectively.[3][4] It shows only negligible efficacy as a releaser of serotonin, with an EC50 value of 2558 nM.[3]

3-FPM also inhibits uptake mediated by dopamine transporters and norepinephrine transporters in HEK293 cells with potencies comparable to cocaine (IC50 values < 2.5 μM), but with less potent effects at serotonin transporters (IC50 values >80 μM).[4]

At sufficient doses, 3-FPM is capable of reversing monoamine transporters, particularly transporters of the catecholamines dopamine and norepinephrine, and, to a much lesser degree, serotonin transporters, thereby releasing these neurotransmitters from the cytosol into the extracellular space, where they are active.[4]

Evaluation of its metabolic pathway revealed N‐oxidation, aryl hydroxylation and subsequent O‐methylation, alkyl hydroxylation, oxidation, and degradation of the ethyl‐bridge yielding the O/N‐bis‐dealkylated metabolite, combinations thereof and further glucuronidation or sulfations.[5]

Legality

In the United States, 3-fluorophenmetrazine is not explicitly illegal at the federal level. However, on November 16, 2016, it became an illegal substance in the state of Virginia.[6] Pursuant to subsection D of § 54.1-3443 of the Code of Virginia, the state Board of Pharmacy designated it as a Schedule I controlled substance, effective through May 10, 2018.[7] Although the initial regulatory period has lapsed, during their 2019 legislative session, the Virginia state legislature is set to vote on a bill that would permanently schedule 3-fluorophenmetrazine as an illegal, Schedule I substance, and it is likely that the bill will succeed. [8]

Sweden's public health agency suggested to classify 3-Fluorophenmetrazine as illegal narcotic on June 1, 2015.[9] It was finally classified on October 15, 2015.[10]

3-Fluorophenmetrazine is illegal in Switzerland as of December 2015.[11]

See also

References
  1. McLaughlin G, Morris N, Kavanagh PV, Dowling G, Power JD, Twamley B, et al. (March 2017). "Test purchase, synthesis and characterization of 3-fluorophenmetrazine (3-FPM) and differentiation from its ortho- and para-substituted isomers" (PDF). Drug Testing and Analysis. 9 (3): 369–377. doi:10.1002/dta.1945. PMID 26810957. S2CID 205762700.
  2. Bäckberg M, Westerbergh J, Beck O, Helander A (November 2016). "Adverse events related to the new psychoactive substance 3-fluorophenmetrazine - results from the Swedish STRIDA project". Clinical Toxicology. 54 (9): 819–825. doi:10.1080/15563650.2016.1211288. PMID 27491700. S2CID 26118285.
  3. Bruce E. Blough; Richard Rothman; Antonio Landavazo; Kevin M. Page; Ann Marie Decker (8 August 2013). "US Patent 20130203752 A1 – Phenylmorpholines and analogues thereof".
  4. Mayer FP, Burchardt NV, Decker AM, Partilla JS, Li Y, McLaughlin G, et al. (May 2018). "Fluorinated phenmetrazine "legal highs" act as substrates for high-affinity monoamine transporters of the SLC6 family". Neuropharmacology. 134 (Pt A): 149–157. doi:10.1016/j.neuropharm.2017.10.006. PMC 7294773. PMID 28988906.
  5. Mardal M, Miserez B, Bade R, Portolés T, Bischoff M, Hernández F, Meyer MR (September 2016). "3-Fluorophenmetrazine, a fluorinated analogue of phenmetrazine: Studies on in vivo metabolism in rat and human, in vitro metabolism in human CYP isoenzymes and microbial biotransformation in Pseudomonas Putida and wastewater using GC and LC coupled to (HR)-MS techniques". Journal of Pharmaceutical and Biomedical Analysis. 128: 485–495. doi:10.1016/j.jpba.2016.06.011. PMID 27372653.
  6. "VA.R. Doc. No. R17-4746". 17 December 2018.
  7. "Va. Code § 54.1-3446". 17 December 2018.
  8. "Senate Bill No. 436". 17 December 2018.
  9. "23 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. 1 June 2015.
  10. "Nya substanser klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. 18 August 2015.
  11. "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Der Bundesrat.
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