4-Fluoroamphetamine

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4-Fluoroamphetamine
4-fluoroamphetamine.svg
4-Fluoroamphetamine molecule ball.png
Clinical data
Pregnancy
category
  • N
Routes of
administration 		By mouth
Legal status
Legal status
Identifiers
  • (RS)-1-(4-Fluorophenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
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KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C9H12FN
Molar mass 153.200 g·mol−1
3D model (JSmol)
  • Fc1ccc(cc1)CC(N)C
  • InChI=1S/C9H12FN/c1-7(11)6-8-2-4-9(10)5-3-8/h2-5,7H,6,11H2,1H3 Yes check.svgY
  • Key:DGXWNDGLEOIEGT-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

4-Fluoroamphetamine (4-FA; 4-FMP; PAL-303; "Flux"), also known as para-fluoroamphetamine (PFA) is a psychoactive research chemical of the phenethylamine and substituted amphetamine chemical classes. It produces stimulant and entactogenic effects. As a recreational drug, 4-FA is sometimes sold along with related compounds such as 2-fluoroamphetamine and 4-fluoromethamphetamine. [2] [3]

Contents

Usage

4-Fluoroamphetamine 4-Fluoroamphetamine.jpg
4-Fluoroamphetamine

4-FA is popular in the Netherlands where it is predominantly used for its specific effects (77% of users) rather than its legal status (18%). [4] 4-FA has become illegal since May 2017. [5]

Effects

The subjective effects of 4-fluoroamphetamine include euphoria which some find similar to the effects of MDMA and amphetamine, [4] increased energy (stimulation), mood elevation, feelings of warmth and empathy, excessive talking, bruxism, and suppressed appetite (anorexic). The general course of effects involves primarily empathogenic effects for the first few hours, which fades out as increased stimulation develops over the next several hours. [ medical citation needed ]

The dopamine reuptake inhibition produced by 4-FA is stronger than that of either 4-CA or 4-IA. [6] 4-FA also produces less hyperthermia than similar compounds such as PMA, 4-MTA and 4-methylamphetamine.[ medical citation needed ]

Common acute side effects are nausea, headaches, increased heart rate and insomnia.[ medical citation needed ]

Chemistry

4-FA reacts with reagent testing to give a semi-unique array of colors which can be used to aid its identification.

Final colors produced by reagent tests
ReagentReaction color
Marquis No reaction [7]
Mandelin Pale Blue [7] [8]
Liebermann Orange [7] [8]
Froehde Faint purple/brown [7] or no reaction.

Pharmacology

4-Fluoroamphetamine is a releasing agent and reuptake inhibitor of dopamine, serotonin, and norepinephrine. [9] The respective EC50 values are 2.0 x 10−7 M, 7.3 x 10−7 M, and 0.37 x 10−7 M, while the IC50 values are 7.7 x 10−7 M, 68 x 10−7 M, and 4.2 x 10−7 M. [3]

4-Fluoroamphetamine has been found to be a weak monoamine oxidase A (MAO-A) inhibitor, with an IC50 Tooltip half-maximal inhibitory concentration of 16,000 nM. [10] For comparison, the IC50 Tooltip half-maximal inhibitory concentration of amphetamine for MAO-A inhibition was 11,000 nM. [10]

Regarding the metabolic fate of 4-FA, the C-F bond at the 4-position on the phenyl ring likely resists deactivation in the liver by cytochrome P450 oxidase. [11] [12]

Neurotoxicity

4-FA does not cause long-lasting depletion of brain serotonin, unlike its analogs 4-CA and 4-BA. [13] This is thought to "reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines." [14]

Neurotoxicity does not increase down the series of para-halogenated amphetamine derivatives, even though serotonin releasing potency does follow this trend. For example, 4-iodoamphetamine is less toxic than is 4-chloroamphetamine. [6] [15] Hence, this property is not related to serotonin releasing potency as such, since PAL-287 was reported to be not at all neurotoxic even though it is a powerful 5-HT releasing agent. [16] It is unclear where 4-methylamphetamine fits in on the neurotoxicity scale. The extensive serotonergic neurotoxicity of 4-chloroamphetamine (and its brominated derivative), and the increased serotonergic toxicity of 4-methylamphetamine [17] suggest that para-substitution seems to increase overall serotonergic (neuro)toxicity, compared to amphetamine. Exceptions include 4-MTA, a para-substituted, non-neurotoxic amphetamine. [18] [19] [20]

Toxicology

The LD50 (mouse; i.p.) of 4-FA is 46 mg/kg. [21]

Fluoroamphetamine (isomer not determined) in a capsule mixed with 25C-NBOMe was associated with three deaths in Melbourne in 2017. [22]

As of October 2015, 4-FA is a controlled substance in China. [23] 4-FA is banned in the Czech Republic. [24] As of 25 May 2017 4-FA is a controlled substance in the Netherlands. [25] 4-FA is also controlled in Australia, Belgium, UK, Germany, Israel, Slovakia, Bulgaria, Chile, Brazil, Canada, Croatia, Sweden, New Zealand and France.[ citation needed ]

Finland

Scheduled in the "government decree on narcotic substances, preparations and plants" and is therefore illegal. [26]

See also

Related Research Articles

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para-Methoxyamphetamine (PMA), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or entactogen effects, and behaves more like an antidepressant in comparison, though it does have some psychedelic properties.

<span class="mw-page-title-main">4-Methylthioamphetamine</span> Chemical compound

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<span class="mw-page-title-main">Naphthylaminopropane</span> Chemical compound

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<span class="mw-page-title-main">5-Fluoro-AMT</span> Chemical compound

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<i>para</i>-Chloroamphetamine Chemical compound

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a serotonin–norepinephrine–dopamine releasing agent (SNDRA) and serotonergic neurotoxin of the amphetamine family. It is used in scientific research in the study of the serotonin system, as a serotonin releasing agent (SRA) at lower doses to produce serotonergic effects, and as a serotonergic neurotoxin at higher doses to produce long-lasting depletions of serotonin.

<span class="mw-page-title-main">MDAI</span> Chemical compound

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<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; monoamine releasing agents can induce the release of one or more of these neurotransmitters.

<span class="mw-page-title-main">3-Methoxy-4-methylamphetamine</span> Entactogen and psychedelic drug of the phenethylamine and amphetamine classes

3-Methoxy-4-methylamphetamine (MMA) is an entactogen and psychedelic drug of the phenethylamine and amphetamine classes. It was first synthesized in 1970 and was encountered as a street drug in Italy in the same decade. MMA was largely forgotten until being reassayed by David E. Nichols as a non-neurotoxic MDMA analogue in 1991, and has subsequently been sold as a designer drug on the internet since the late 2000s.

<span class="mw-page-title-main">MMAI</span> Chemical compound

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<span class="mw-page-title-main">5-IAI</span> Chemical compound

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<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

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<span class="mw-page-title-main">4-Methylamphetamine</span> Stimulant and anorectic drug of the amphetamine class

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<i>para</i>-Iodoamphetamine Chemical compound

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α-Methyldopamine Chemical compound

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<span class="mw-page-title-main">3-Methylamphetamine</span> Stimulant drug of the amphetamine class

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<span class="mw-page-title-main">3-Fluoroamphetamine</span> Stimulant drug that acts as an amphetamine

3-Fluoroamphetamine is a stimulant drug from the amphetamine family which acts as a monoamine releaser with similar potency to methamphetamine but more selectivity for dopamine and norepinephrine release over serotonin. It is self-administered by mice to a similar extent to related drugs such as 4-fluoroamphetamine and 3-methylamphetamine.

<span class="mw-page-title-main">3-Methoxyamphetamine</span> Stimulant drug of the amphetamine class

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<span class="mw-page-title-main">5-Chloro-αMT</span> Chemical compound

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<i>para</i>-Chloromethamphetamine Chemical compound

para-Chloromethamphetamine is a stimulant that is the N-methyl derivative and prodrug of the neurotoxic drug para-chloroamphetamine (4-CA). It has been found to decrease serotonin in rats. Further investigation into the long-term effects of chloroamphetamines discovered that administration of 4-CMA caused a prolonged reduction in the levels of serotonin and the activity of tryptophan hydroxylase in the brain one month after injection of a single dose of the drug.

References

  1. ↑ "Substance Details 4-Fluoroamphetamine" . Retrieved 22 January 2024.
  2. ↑ Rösner P, Quednow B, Girreser U, Junge T (March 2005). "Isomeric fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs)". Forensic Science International. 148 (2–3): 143–156. CiteSeerX   10.1.1.670.7372 . doi:10.1016/j.forsciint.2004.05.003. PMID   15639609.
  3. 1 2 Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID   17223101.
  4. 1 2 Linsen F, Koning RP, van Laar M, Niesink RJ, Koeter MW, Brunt TM (July 2015). "4-Fluoroamphetamine in the Netherlands: more than a one-night stand". Addiction. 110 (7): 1138–1143. doi:10.1111/add.12932. PMID   25808511.
  5. ↑ "Het is nu officieel: de partydrug 4-FA is verboden". nos.nl. 25 May 2017. Archived from the original on 24 August 2017.
  6. 1 2 Marona-Lewicka D, Rhee GS, Sprague JE, Nichols DE (December 1995). "Psychostimulant-like effects of p-fluoroamphetamine in the rat". European Journal of Pharmacology. 287 (2): 105–113. doi:10.1016/0014-2999(95)00478-5. PMID   8749023.
  7. 1 2 3 4 "4-FA reaction colour results with liebermann and froehde reagent test kits". Reagent Tests UK. 3 January 2016. Archived from the original on 14 February 2016. Retrieved 14 February 2016.
  8. 1 2 Uchiyama N, Kawamura M, Kamakura H, Kikura-Hanajiri R, Goda Y (June 2008). "[Analytical data of designated substances (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan, part II: Color test and TLC]". Yakugaku Zasshi. 128 (6): 981–987. doi: 10.1248/yakushi.128.981 . PMID   18520145. Archived from the original on 5 March 2016.
  9. ↑ Toennes SW, Schneider D, Pogoda W, Paulke A, Wunder C, Theunissen EL, et al. (July 2019). "Pharmacokinetic properties of 4-fluoroamphetamine in serum and oral fluid after oral ingestion". Drug Testing and Analysis. 11 (7): 1028–1034. doi:10.1002/dta.2595. PMID   30912312. S2CID   85518011.
  10. 1 2 Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10: 1590. doi: 10.3389/fphar.2019.01590 . PMC   6989591 . PMID   32038257.
  11. ↑ Fisher MB, Henne KR, Boer J (January 2006). "The complexities inherent in attempts to decrease drug clearance by blocking sites of CYP-mediated metabolism". Current Opinion in Drug Discovery & Development. 9 (1): 101–109. PMID   16445122.
  12. ↑ Toennes SW, Schneider D, Pogoda W, Paulke A, Wunder C, Theunissen EL, et al. (July 2019). "Pharmacokinetic properties of 4-fluoroamphetamine in serum and oral fluid after oral ingestion". Drug Testing and Analysis. 11 (7): 1028–1034. doi:10.1002/dta.2595. PMID   30912312. S2CID   85518011.
  13. ↑ Harvey JA (June 1978). "Neurotoxic action of halogenated amphetamines". Annals of the New York Academy of Sciences. 305 (1): 289–304. Bibcode:1978NYASA.305..289H. doi:10.1111/j.1749-6632.1978.tb31530.x. PMID   81648. S2CID   38386908.
  14. ↑ Fuller RW, Baker JC, Perry KW, Molloy BB (October 1975). "Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: drug levels in brain and effects on brain serotonin metabolism". Neuropharmacology. 14 (10): 739–746. doi:10.1016/0028-3908(75)90099-4. PMID   1196472. S2CID   9620299.
  15. ↑ Nichols DE, Johnson MP, Oberlender R (January 1991). "5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine". Pharmacology, Biochemistry, and Behavior. 38 (1): 135–139. CiteSeerX   10.1.1.670.504 . doi:10.1016/0091-3057(91)90601-W. PMID   1826785. S2CID   20485505.
  16. ↑ Rothman RB, Blough BE, Woolverton WL, Anderson KG, Negus SS, Mello NK, et al. (June 2005). "Development of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration". The Journal of Pharmacology and Experimental Therapeutics. 313 (3): 1361–1369. doi:10.1124/jpet.104.082503. PMID   15761112. S2CID   19802702.
  17. ↑ Blanckaert P, van Amsterdam J, Brunt T, van den Berg J, Van Durme F, Maudens K, van Bussel J (September 2013). "4-Methyl-amphetamine: a health threat for recreational amphetamine users". Journal of Psychopharmacology. 27 (9): 817–822. doi:10.1177/0269881113487950. PMID   23784740. S2CID   35436194.
  18. ↑ Huang X, Marona-Lewicka D, Nichols DE (December 1992). "p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent". European Journal of Pharmacology. 229 (1): 31–38. doi:10.1016/0014-2999(92)90282-9. PMID   1473561.
  19. ↑ Li Q, Murakami I, Stall S, Levy AD, Brownfield MS, Nichols DE, Van de Kar LD (December 1996). "Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAi) and p-methylthioamphetamine (MTA)". The Journal of Pharmacology and Experimental Therapeutics. 279 (3): 1261–1267. PMID   8968349.
  20. ↑ Murphy J, Flynn JJ, Cannon DM, Guiry PJ, McCormack P, Baird AW, et al. (May 2002). "In vitro neuronal and vascular responses to 5-hydroxytryptamine: modulation by 4-methylthioamphetamine, 4-methylthiomethamphetamine and 3,4-methylenedioxymethamphetamine". European Journal of Pharmacology. 444 (1–2): 61–67. doi:10.1016/S0014-2999(02)01586-8. PMID   12191583.
  21. ↑ Costa E, Garattini S (1970). Amphetamines and Related Compounds. New York: Raven Press. p. 28.
  22. ↑ "News: March 2017 – Australia: "Ecstasy" capsules containing NPS are related to several deaths and severe intoxications in Melbourne". www.unodc.org. Retrieved 27 February 2022.
  23. ↑ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
  24. ↑ "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)" (PDF) (in Czech). Ministerstvo zdravotnictví. Archived (PDF) from the original on 9 March 2016.
  25. ↑ Van der Velden L (25 May 2017). "Vanaf vandaag is partydrug 4-FA officieel verboden - maar of dat helpt?" (in Dutch). de Volkskrant. Archived from the original on 25 May 2017. Retrieved 25 May 2017.
  26. ↑ https://finlex.fi/fi/laki/ajantasa/2008/20080543
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