3-Fluoroamphetamine

Last updated

3-Fluoroamphetamine
3-fluoroamphetamine.svg
3-Fluoroamphetamine molecule ball.png
Clinical data
Trade names 3FPPA
Addiction
liability 		moderate [1]
Routes of
administration 		Oral
Legal status
Legal status
Pharmacokinetic data
Onset of action 20 - 60 minutes
Elimination half-life 90 minutes
Duration of action 2 - 3 hours "3-FA". Psychonautwiki.[ unreliable medical source? ]
Identifiers
  • (RS)-1-(3-Fluorophenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C9H12FN
Molar mass 153.200 g·mol−1
3D model (JSmol)
Density 1.0 [2]  g/cm3
Boiling point 208.2 [2]  °C (406.8 °F)
  • Fc1cccc(c1)CC(C)N
  • InChI=1S/C9H12FN/c1-7(11)5-8-3-2-4-9(10)6-8/h2-4,6-7H,5,11H2,1H3 Yes check.svgY
  • Key:PIOCLGPCMNPZFT-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

3-Fluoroamphetamine (3-FA; PAL-353) 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. [3] It is self-administered by mice to a similar extent to related drugs such as 4-fluoroamphetamine and 3-methylamphetamine. [4]

Contents

3-Fluoroamphetamine often found its use as a designer drug in several studies to mimic the effects of illegal amphetamines. [5] It has also appeared on the drug market for recreational use as an amphetamine alternative, its has been reported in January 2009 to the European Early Warning System by Belgium. Little is known about the exact history of this compound. [6]

Chemistry

3-Fluoroamphetamine is a synthetic molecule of the substituted amphetamine class. Molecules in this class contain a phenethylamine core that consists of a phenyl ring, ethyl chain, a terminal amino (NH2) group and a methyl substitution at Rα. Amphetamines themselves belong to the class of alpha-methylated phenethylamines.[ citation needed ] Substituted amphetamines can be synthesised by substituting a hydrogen atom with a substituent which in 3-fluoroamphetamines case is a fluorine atom positioned on the third carbon of the phenyl ring.3-Fluoroamphetamine has a chemical formula of C9H12FN. At room temperature it is a liquid with molecular mass of 153.200 g·mol−1. [7]

Pharmacology

3-Fluoroamphetamine is a locomotor stimulant that acts as a substrate-based releaser, with selectivity for dopamine over serotonin. This rank order is about the same as for amphetamine when tested in non-human primates. [8] The halflife was also comparable to amphetamine when tested in rats, namely 91 minutes. 3-Fluoroamphetamine is a good candidate for transdermal administration since it is a relatively small molecule with a low melting point, has a weak basicity (pKa of 10) and is moderately lipophilic. These properties make it easier to get through the stratum corneum, which is the lipid-rich outermost barrier of the skin. [9] By replacing a hydrogen in the ring with a fluorine, the compound is more likely to permeate the blood brain barrier. The P450 oxidase metabolism will most likely oxidize the 3-fluoroamphetamine at the 4 position, creating 3-fluoro-4-hydroxyamphetamine which is hypothesized to be aversive to the intake of stimulants. [10]

Molecular mechanism

Like other amphetamine derivatives, 3-fluoroamphetamine acts as a monoamine releaser with a higher selectivity for dopamine and norepinephrine over serotonin. [11] There are multiple targets at which amphetamines can disrupt the normal function of these neurotransmitters. First, 3-fluoroamphetamine can interact with their respective transmembrane monoamine transporters DAT, NET, and SERT to mediate neurotransmitter release and reuptake. [10] It does this by blocking these transmembrane transporters, which usually transport monoamines back into the presynapse from the synaptic cleft. Blocking of DAT, NET, and SERT causes prolonged elevated concentrations of dopamine, norepinephrine, and serotonin in the synaptic cleft, causing more stimulant effects associated with these neurotransmitters.[ citation needed ]

Another way for amphetamine derivatives to influence neurotransmission is by entering the presynapse via DAT, NET, and SERT, where the amphetamine derivative accumulates inside the neuron and replaces monoamines in synaptic vesicles by interacting with vesicular monoamine transporter VMAT2. The concentration of free monoamines in the presynapse increases, prohibiting the inward transport of monoamines and encouraging the outward transport. Furthermore, amphetamine derivatives inhibit the action of mitochondrial monoamine oxidases (MOA), which catalyze the degradation of cytosolic monoamines. Inhibition thus increases cytosolic concentrations of monoamines even more. [12]

The mechanism of action for 3-fluoroamphetamine has not been individually studied yet, but various sources suggest that amphetamine derivatives generally have the same mechanism of action in monoaminergic neurons . [12] However, further investigation on 3-fluoroamphetamine could reveal more specific mechanisms in which this amphetamine derivative modulates‌ processes within the body.

Uses

3-Fluoroamphetamine is distinguished by its potent stimulant and mild entactogenic effects, setting it apart from other amphetamines such as 4-FA, 2-FA, and 2-FMA. It lacks the productivity and focus-enhancing properties reported for 2-FA and 2-FMA, potentially limiting its appeal and availability.[ citation needed ] Beyond its recreational use, 3-fluoroamphetamine has been identified as a nonselective inhibitor of dopamine and serotonin reuptake, with research suggesting its potential to inhibit cancer cell proliferation in vitro and promote the release of growth factors in neural contexts. [13] [14] These findings point to its utility in neuropharmacological research and possible applications in treating obesity, cancer, and cocaine dependency. [14] [1]

China

As of October 2015 3-fluoroamphetamine is a controlled substance in China. [15]

Germany

3-Fluoroamphetamine is controlled under the NpSG (New Psychoactive Substances Act) [16] as of November 26, 2016. [17] Production and import with the aim to place it on the market, administration to another person and trading is punishable.

New Zealand

3-Fluoroamphetamine is an amphetamine analogue, so is a Schedule 3 Class C controlled substance in New Zealand. [18]

Switzerland

3-Fluoroamphetamine is a controlled substance specifically named under Verzeichnis E. [19]

Turkey

3-Fluoroamphetamine is a classed as drug and is illegal to possess, produce, supply, or import. [20]

United Kingdom

3-Fluoroamphetamine is considered a Class A drug as a result of the amphetamine analogue clause of the Misuse of Drugs Act 1971. [21]

United States: 3-Fluoroamphetamine may be considered to be an analog of amphetamine, thus falling under the Federal Analogue Act. The Federal Analogue Act, 21 U.S.C. § 813, is a section of the United States Controlled Substances Act, allowing any chemical "substantially similar" to an illegal drug (in Schedule I or II) to be treated as if it were also in Schedule I or II, but only if it is intended for human consumption.

See also

Related Research Articles

<span class="mw-page-title-main">Monoamine transporter</span> Proteins that function as integral plasma-membrane transporters

Monoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and post-translational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

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

4-Fluoroamphetamine, 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.

<span class="mw-page-title-main">Chlorphentermine</span> Weight loss medication

Chlorphentermine, sold under the brand names Apsedon, Desopimon, and Lucofen, is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the para-chloro derivative of the better-known appetite suppressant phentermine, which is still in current use.

<span class="mw-page-title-main">Phenyltropane</span> Class of chemical compounds

Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. This research has spanned beyond the last couple decades, and has picked up its pace in recent times, creating numerous phenyltropanes as research into cocaine analogues garners interest to treat addiction.

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

Naphthylaminopropane (PAL-287) is an experimental drug under investigation as of 2007 for the treatment of alcohol and stimulant addiction.

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

5-Methyl-3,4-methylenedioxyamphetamine (5-Methyl-MDA) is an entactogen and psychedelic designer drug of the amphetamine class. It is a ring-methylated homologue of MDA and a structural isomer of MDMA.

<span class="mw-page-title-main">RTI-336</span> Chemical compound

RTI(-4229)-336, is a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug. It binds to the dopamine transporter with around 20x the affinity of cocaine, however it produces relatively mild stimulant effects, with a slow onset and long duration of action. These characteristics make it a potential candidate for treatment of cocaine addiction, as a possible substitute drug analogous to how methadone is used for treating heroin abuse. RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration, and significantly reduces rates of cocaine use, especially when combined with SSRIs, and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.

<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 activity as a monoaminergic neurotoxin, 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, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen drug of the 2-aminoindane group which is related to MDMA and produces similar subjective effects.

<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.

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.

<span class="mw-page-title-main">RTI-112</span> Chemical compound

RTI(-4229)-112 is a synthetic stimulant drug from the phenyltropane family. In contrast to RTI-113, which is DAT selective, RTI-112 is a nonselective triple reuptake inhibitor.

<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.

<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-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">3-Fluoroethamphetamine</span> Stimulant drug of the amphetamine class

3-Fluoroethamphetamine (3-FEA) is a stimulant drug of the amphetamine class which acts as a releasing agent of the monoamine neurotransmitters norepinephrine, dopamine and serotonin.

<span class="mw-page-title-main">RTI-83</span> Chemical compound

RTI-83 is a phenyltropane derivative which represents a rare example of an SDRI or serotonin-dopamine reuptake inhibitor, a drug which inhibits the reuptake of the neurotransmitters serotonin and dopamine, while having little or no effect on the reuptake of the related neurotransmitter noradrenaline. With a binding affinity (Ki) of 55 nM at DAT and 28.4 nM at SERT but only 4030 nM at NET, RTI-83 has reasonable selectivity for DAT/SERT over NET

<span class="mw-page-title-main">Serotonin–dopamine reuptake inhibitor</span> Class of drug

A serotonin–dopamine reuptake inhibitor (SDRI) is a type of drug which acts as a reuptake inhibitor of the monoamine neurotransmitters serotonin and dopamine by blocking the actions of the serotonin transporter (SERT) and dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of serotonin and dopamine, and, therefore, an increase in serotonergic and dopaminergic neurotransmission.

A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.

<span class="mw-page-title-main">2-Fluoromethcathinone</span> Designer stimulant

2-Fluoromethcathinone (2-FMC), also known as 2-flephedrone, is a psychostimulant and designer drug of the cathinone family. It acts as a dopamine and norepinephrine releasing agent (NDRA).

References

  1. 1 2 Puri A, Murnane KS, Blough BE, Banga AK (August 2017). "Effects of chemical and physical enhancement techniques on transdermal delivery of 3-fluoroamphetamine hydrochloride". International Journal of Pharmaceutics. 528 (1–2): 452–462. doi:10.1016/j.ijpharm.2017.06.041. PMID   28633107.
  2. 1 2 "3-Fluoroamphetamine | C9H12FN". Chemspider. 2022.
  3. ↑ Negus SS, Mello NK, Blough BE, Baumann MH, Rothman RB (February 2007). "Monoamine releasers with varying selectivity for dopamine/norepinephrine versus serotonin release as candidate "agonist" medications for cocaine dependence: studies in assays of cocaine discrimination and cocaine self-administration in rhesus monkeys". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 627–36. doi:10.1124/jpet.106.107383. PMID   17071819. S2CID   8326027.
  4. ↑ Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL (May 2005). "Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs". The Journal of Pharmacology and Experimental Therapeutics. 313 (2): 848–54. doi:10.1124/jpet.104.080101. PMID   15677348. S2CID   12135483.
  5. ↑ Seibert E, Mader E, Schmid MG (November 2021). "A simple and isocratic protein-based high performance liquid chromatography method for the enantioseparation of amphetamine derivatives". Journal of Chromatography Open. 1: 100013. doi: 10.1016/j.jcoa.2021.100013 . ISSN   2772-3917.
  6. ↑ "GLOBAL SMART UPDATE 2009 Volume 2" (PDF). www.unodc.org. United Nations Office on Drugs and Crime. October 1, 2009.
  7. ↑ "1-(3-Fluorophenyl)propan-2-amine 3D-FF36292". CymitQuimica. Retrieved 2024-03-14.
  8. ↑ Kimmel HL, Manvich DF, Blough BE, Negus SS, Howell LL (December 2009). "Behavioral and neurochemical effects of amphetamine analogs that release monoamines in the squirrel monkey". Pharmacology, Biochemistry, and Behavior. 94 (2): 278–284. doi:10.1016/j.pbb.2009.09.007. PMC   2763934 . PMID   19766133.
  9. ↑ Jiang Y, Ray A, Junaid MS, Bhattaccharjee SA, Kelley K, Banga AK, et al. (February 2020). "The pharmacokinetics of 3-fluoroamphetamine following delivery using clinically relevant routes of administration". Drug Delivery and Translational Research. 10 (1): 271–281. doi:10.1007/s13346-019-00685-4. PMC   6982562 . PMID   31642004.
  10. 1 2 Carroll FI, Lewin AH, Mascarella SW, Seltzman HH, Reddy PA (April 2021). "Designer drugs: a medicinal chemistry perspective (II)". Annals of the New York Academy of Sciences. 1489 (1): 48–77. doi:10.1111/nyas.14349. PMID   32396701.
  11. ↑ Negus SS, Mello NK, Blough BE, Baumann MH, Rothman RB (February 2007). "Monoamine releasers with varying selectivity for dopamine/norepinephrine versus serotonin release as candidate "agonist" medications for cocaine dependence: studies in assays of cocaine discrimination and cocaine self-administration in rhesus monkeys". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 627–636. doi:10.1124/jpet.106.107383. PMID   17071819.
  12. 1 2 Sitte HH, Freissmuth M (January 2015). "Amphetamines, new psychoactive drugs and the monoamine transporter cycle". Trends in Pharmacological Sciences. 36 (1): 41–50. doi:10.1016/j.tips.2014.11.006. PMC   4502921 . PMID   25542076.
  13. ↑ Gao Y, Du L, Li Q, Li Q, Zhu L, Yang M, et al. (July 2022). "How physical techniques improve the transdermal permeation of therapeutics: A review". Medicine. 101 (26): e29314. doi:10.1097/MD.0000000000029314. PMC   9239599 . PMID   35777055.
  14. 1 2 "FF36292 1-(3-Fluorophenyl)propan-2-amine Datasheets". www.biosynth.com. Retrieved 2024-03-14.
  15. ↑ "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.
  16. ↑ "Anlage NpSG - Einzelnorm". www.gesetze-im-internet.de (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved 2024-03-14.
  17. ↑ "Bundesgesetzblatt BGBl. Online-Archiv 1949 - 2022 | Bundesanzeiger Verlag" (PDF). www.bgbl.de (in German). Retrieved 2024-03-14.
  18. ↑ "Misuse of Drugs Act 1975 No 116". legislation.govt.nz. July 1, 2022.
  19. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland].
  20. ↑ "Başbakanlık Mevzuatı Geliştirme ve Yayın Genel Müdürlüğü". resmigazete.gov.tr (in Turkish). Retrieved 2024-03-14.
  21. ↑ "Misuse of Drugs Act 1971".
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