4-Fluoroamphetamine

Last updated

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
UNII
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, 3-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]

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. [10] [11]

Neurotoxicity

4-FA does not cause long-lasting depletion of brain serotonin, unlike its analogs 4-CA and 4-BA. [12] This is thought to "reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines." [13]

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] [14] 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. [15] 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 [16] suggest that para-substitution seems to increase overall serotonergic (neuro)toxicity, compared to amphetamine. Exceptions include 4-MTA, a para-substituted, non-neurotoxic amphetamine. [17] [18] [19]

Toxicology

The LD50 (mouse; i.p.) of 4-FA is 46 mg/kg. [20]

Fluoroamphetamine (isomer not determined) in a capsule mixed with 25C-NBOMe was associated with three deaths in Melbourne in 2017. [21]

As of October 2015, 4-FA is a controlled substance in China. [22] 4-FA is banned in the Czech Republic. [23] As of 25 May 2017 4-FA is a controlled substance in the Netherlands. [24] 4-FA is also controlled in Australia, Belgium, UK, Germany, Israel, Slovakia, Bulgaria, Chile, Brazil, Canada, Croatia, Sweden, New Zealand and France.[ citation needed ]

See also

Related Research Articles

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

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

4-Methylthioamphetamine (4-MTA) is a designer drug of the substituted amphetamine class developed in the 1990s by a team led by David E. Nichols, an American pharmacologist and medical chemist, at Purdue University. It acts as a non-neurotoxic highly selective serotonin releasing agent (SSRA) in animals. 4-MTA is the methylthio derivative of amphetamine.

<i>meta</i>-Chlorophenylpiperazine Stimulant

meta-Chlorophenylpiperazine (mCPP) is a psychoactive drug of the phenylpiperazine class. It was initially developed in the late-1970s and used in scientific research before being sold as a designer drug in the mid-2000s. It has been detected in pills touted as legal alternatives to illicit stimulants in New Zealand and pills sold as "ecstasy" in Europe and the United States.

<span class="mw-page-title-main">4-Bromomethcathinone</span> Psychoactive drug and research chemical

4-Bromomethcathinone is a psychoactive drug and research chemical of the phenethylamine, amphetamine, and cathinone chemical classes. It acts as a serotonin and norepinephrine reuptake inhibitor, but acts more like an antidepressant than a stimulant. Some 4-halogenated cathinones seem to share the selective serotonergic neurotoxicity of their corresponding amphetamine analogues.

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

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a substituted amphetamine and monoamine releaser similar to MDMA, but with substantially higher neurotoxicity, thought to be due to the unrestrained release of both serotonin and dopamine by a metabolite. It is used as a neurotoxin by neurobiologists to selectively kill serotonergic neurons for research purposes, in the same way that 6-hydroxydopamine is used to kill dopaminergic neurons.

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

MDAI (5,6-methylenedioxy-2-aminoindane) is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) in vitro and produces entactogen effects in humans.

<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 (decade).

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

5-Methoxy-6-methyl-2-aminoindane (MMAI) is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) and produces entactogen effects in humans. It has been sold as a designer drug and research chemical online since 2010.

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

5-Iodo-2-aminoindane (5-IAI) is a drug which acts as a releasing agent of serotonin, norepinephrine, and dopamine. It was developed in the 1990s by a team led by David E. Nichols at Purdue University. 5-IAI fully substitutes for MDMA in rodents and is a putative entactogen in humans. Unlike related aminoindane derivatives like MDAI and MMAI, 5-IAI causes some serotonergic neurotoxicity in rats, but is substantially less toxic than its corresponding amphetamine homologue pIA, with the damage observed barely reaching statistical significance.

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons.

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

Ortetamine (INN), also known as 2-methylamphetamine, is a stimulant drug of the amphetamine class. In animal drug discrimination tests it substituted for dextroamphetamine more closely than either 3- or 4-methylamphetamine, although with only around 1/10 the potency of dextroamphetamine itself.

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

4-Methylamphetamine is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes.

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

para-Bromoamphetamine (PBA), also known as 4-bromoamphetamine (4-BA), is an amphetamine derivative which acts as a serotonin-norepinephrine-dopamine releasing agent (SNDRA) and produces stimulant effects.

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

para-Iodoamphetamine (PIA), also known as 4-iodoamphetamine (4-IA), is a research chemical of the phenethylamine and amphetamine chemical classes.

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

3-Methylamphetamine is a stimulant drug from the amphetamine family. It is self-administered by mice to a similar extent to 4-fluoroamphetamine and has comparable properties as a monoamine releaser, although with a more balanced release of all three monoamines, as opposed to the more dopamine/noradrenaline selective fluoro analogues.

<span class="mw-page-title-main">3-Fluoroamphetamine</span> Stimulant drug

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

meta-Methoxyamphetamine (MMA), also known as 3-methoxyamphetamine (3-MA), is a stimulant drug from the amphetamine family. It has similar effects in animal drug discrimination tests to the more widely known derivative 4-methoxyamphetamine (PMA), although with a slightly different ratio of monoamine release, being a combined serotonin, dopamine, and norepinephrine releasing agent rather than a fairly selective serotonin releaser like PMA. 3-Methoxyamphetamine has similarly appeared on the illicit market as a designer drug alternative to MDMA, although far more rarely than its infamous positional isomer. It produces gepefrine, a cardiac stimulant, as one of its major metabolites.

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

5-MAPB is an entactogenic designer drug similar to MDMA in its structure and effects.

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

5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known specific serotonin-dopamine releasing agents (SDRAs). It has been investigated in animals as a potential treatment for cocaine dependence. The EC50 values of 5-chloro-αMT in evoking the in vitro release of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in rat synaptosomes were reported as 16 nM, 54 nM, and 3434 nM, with an NE/DA ratio of 63.6 and a DA/5-HT ratio of 3.38, indicating that it is a highly specific and well-balanced SDRA. However, 5-chloro-αMT has also been found to act as a potent full agonist of the 5-HT2A receptor, with an EC50 value of 6.27 nM and an efficacy of 105%, and almost assuredly acts as a potent agonist of other serotonin receptors as well.

<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. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ Costa E, Garattini S (1970). Amphetamines and Related Compounds. New York: Raven Press. p. 28.
  21. ↑ "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.
  22. ↑ "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.
  23. ↑ "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.
  24. ↑ 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.