3-Fluorophenmetrazine

3-Fluorophenmetrazine
Clinical data
Other names	3-FPM, 3-FPH, PAL-593
Legal status
Legal status	BR: Class F2 (Prohibited psychotropics); CA: Unscheduled; DE: NpSG (Industrial and scientific use only); UK: Under Psychoactive Substances Act; US: Unscheduled; ; Not controlled at the federal level, but possibly illegal under Federal Analogue Act of 1986, Schedule I in the state of Virginia; Illegal in Sweden and Switzerland;
Identifiers
	IUPAC name 2-(3-Fluorophenyl)-3-methylmorpholine;
CAS Number	1350768-28-3 ; HCl: 1803562-83-5;
PubChem CID	54673723; HCl: 75481405;
ChemSpider	37509994; HCl: 34212559;
UNII	BEV6RF569G;
CompTox Dashboard (EPA)	DTXSID201032414 ;
Chemical and physical data
Formula	C11H14FNO
Molar mass	195.237 g·mol−1
3D model (JSmol)	Interactive image; HCl: Interactive image;
Boiling point	280.6 °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;

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]

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, but may be considered under the federal analogue act if intended for consumption as a structural analog of the Schedule II drug Phenmetrazine, but only if intended for human consumption.

On November 16, 2016, it became an illegal substance in the state of Virginia.^[6] As of 2019, it is also a schedule I substance in Virginia. The positional isomers of 3-fluorophenmetrazine such as 2-fluorophenmetrazine and 4-fluorophenmetrazine are also illegal under Virginia law,^[7] but not federal law.^[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]

References

^ 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.
^ 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.
^ ^a ^b US 20130203752, Blough BE, Rothman R, Landavazo A, Page KM, Decker AM, "Phenylmorpholines and analogues thereof", issued 8 August 2013
^ ^a ^b ^c 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.
^ 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.
^ "VA.R. Doc. No. R17-4746". 17 December 2018.
^ "§ 54.1-3446. Schedule I." Retrieved 8 September 2023.
^ "21 U.S. Code § 812 - Schedules of controlled substances". 8 September 2023.
^ "23 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. 1 June 2015.
^ "Nya substanser klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. 18 August 2015.
^ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Der Bundesrat.