4-Fluoroamphetamine (4-FA) Cas 459-02-9

4-Fluoroamphetamine (4-FA) Cas 459-02-9

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.

• Chemical Formula: C9H13ClFN
• Molecular Weight: 189.66 g/mol
• Effects: Users report euphoria, increased energy, mood elevation, excessive talking, and suppressed appetite. 

  2
• Legal Status: It has been illegal since May 2017, and its usage has significantly decreased since then. 

  1

  
  For more detailed information, you can refer to the sources(https://www.casbase.org/cas/459-02-9),(https://en.wikipedia.org/wiki/4-Fluoroamphetamine), and(https://www.fishersci.com/us/en/browse/cas/459-02-9)

4-FA was popular in the Netherlands where it was predominantly used for its specific effects (77% of users) rather than its legal status (18%).^[5] 4-FA has become illegal since May 2017.^[6] Since the ban usage has decreased a lot. Accurate statistics of usage are not available until 2020, but submitted samples to get tested were counted. In 2016 1.100 (10%) of samples tested for DIMS were 4-FA samples,^[7] in 2024 less than 50 4-FA samples were submitted.^[8] In 2020 0,3% of Dutch adults used 4-FA in the previous year, in 2024 this was just 0,1%.^[9]

The subjective effects of 4-fluoroamphetamine include euphoria which some find similar to the effects of MDMA and amphetamine,^[5] 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] 4-Fluoroamphetamine (4-FA) Cas 459-02-9}

The dopamine reuptake inhibition produced by 4-FA is stronger than that of either 4-CA or 4-IA.^[10] 4-FA also produces less hyperthermia than similar compounds such as PMA, 4-MTA and 4-methylamphetamine.^{[medical citation needed]}

4-FA has been described as producing a very mild “psychedelic” state, intermediate between that of amphetamine and MDMA.^[11] It is unclear whether this is related to induction of monoamine release or serotonin 5-HT_2A receptor agonism.^[11]

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

4-Fluoroamphetamine (hydrochloride)

Item No. 11156

Restricted Product (Schedule I)

Specification

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

4-Fluoroamphetamine is a releasing agent and reuptake inhibitor of dopamine, serotonin, and norepinephrine.^[14] The respective EC₅₀ values are 200 nM, 730 nM, and 37 nM, while the IC₅₀ values are 770 nM, 6800 nM, and 420 nM.^[4]

The drug shows some affinity for the serotonin 5-HT_2A receptor (K_i = 11,300 nM) and serotonin 5-HT_2C receptor (K_i = 7,800 nM), similar to that of MDMA in the case of the serotonin 5-HT_2A receptor (K_i = 5,900 nM), but far below the affinity of structurally related classical serotonergic psychedelics like 2C-B.^[11][15] It has also been shown to act as a very low-potency serotonin 5-HT_2B receptor partial agonist (EC₅₀Tooltip half-maximal effective concentration = 14,400 nM; E_maxTooltip maximal efficacy = 58%).^[15]

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.^[16] For comparison, the IC₅₀Tooltip half-maximal inhibitory concentration of amphetamine for MAO-A inhibition was 11,000 nM.^[16]

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.^[17][18]

4-FA does not cause long-lasting depletion of brain serotonin, unlike its analogs 4-CA and 4-BA.^[19] This is thought to “reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines.”^[20]

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.^[10][21] 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.^[22] 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^[23] suggest that para-substitution seems to increase overall serotonergic (neuro)toxicity, compared to amphetamine. Exceptions include 4-MTA, a para-substituted, non-neurotoxic amphetamine.^[24][25][26]

The LD₅₀ (mouse; i.p.) of 4-FA is 46 mg/kg.^[27]

Fluoroamphetamine (isomer not determined) in a capsule mixed with 25C-NBOMe was associated with three deaths in Melbourne in 2017.^[28]