4-Fluoroamphetamine

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]

4-Fluoroamphetamine

Clinical data
Pregnancy category	N
Routes of administration	By mouth
Legal status
Legal status	BR: Class F2 (Prohibited psychotropics) CA: Schedule I DE: Anlage I (Authorized scientific use only) UK: Class A UN: Psychotropic Schedule II[1]
Identifiers
IUPAC name (RS)-1-(4-Fluorophenyl)propan-2-amine
CAS Number	459-02-9 N
PubChem CID	9986
ChemSpider	9592 Y
UNII	S5744XYR1Z
KEGG	C22767
CompTox Dashboard (EPA)	DTXSID90894758
Chemical and physical data
Formula	C9H12FN
Molar mass	153.200 g·mol−1
3D model (JSmol)	Interactive image
SMILES Fc1ccc(cc1)CC(N)C
InChI InChI=1S/C9H12FN/c1-7(11)6-8-2-4-9(10)5-3-8/h2-5,7H,6,11H2,1H3 Y Key:DGXWNDGLEOIEGT-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Usage

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

Reagent	Reaction 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 IC₅₀Tooltip half-maximal inhibitory concentration of 16,000 nM.^[10] For comparison, the IC₅₀Tooltip 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]

Legal status

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

• 2-Fluoroamphetamine (2-FA)
• 3-Fluoroamphetamine (3-FA)
• 3,4-Difluoroamphetamine
• 4-Fluoromethamphetamine (4-FMA)
• 4-Fluoromethcathinone (4-FMC)
• 4'-Fluoro-4-methylaminorex
• para-Bromoamphetamine (PBA)
• para-Bromomethamphetamine (PBMA)