4-FA
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.
Chemistry
4-FA reacts with reagent testing to give a semi-unique array of colors which can be used to aid its identification.
| Reagent | Reaction color |
|---|---|
| Marquis | No reaction |
| Mandelin | Pale Blue |
| Liebermann | Orange |
| Froehde | Faint purple/brown or no reaction. |
Pharmacology
4-Fluoroamphetamine is a releasing agent and reuptake inhibitor of dopamine, serotonin, and norepinephrine. The respective EC50 values are 200 nM, 730 nM, and 37 nM, while the IC50 values are 770 nM, 6800 nM, and 420 nM.
The drug shows some affinity for the serotonin 5-HT2A receptor (Ki = 11,300 nM) and serotonin 5-HT2C receptor (Ki = 7,800 nM), similar to that of MDMA in the case of the serotonin 5-HT2A receptor (Ki = 5,900 nM), but far below the affinity of structurally related classical serotonergic psychedelics like 2C-B. It has also been shown to act as a very low-potency serotonin 5-HT2B receptor partial agonist (half-maximal effective concentration“}]]}”>EC50Tooltip half-maximal effective concentration = 14,400 nM; maximal efficacy“}]]}”>EmaxTooltip maximal efficacy = 58%).
4-Fluoroamphetamine has been found to be a weak monoamine oxidase A (MAO-A) inhibitor, with an half-maximal inhibitory concentration“}]]}”>IC50Tooltip half-maximal inhibitory concentration of 16,000 nM. For comparison, the half-maximal inhibitory concentration“}]]}”>IC50Tooltip half-maximal inhibitory concentration of amphetamine for MAO-A inhibition was 11,000 nM.
Neurotoxicity
4-FA does not cause long-lasting depletion of brain serotonin, unlike its analogs 4-CA and 4-BA. This is thought to “reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines.”
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. 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. 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 suggest that para-substitution seems to increase overall serotonergic (neuro)toxicity, compared to amphetamine. Exceptions include 4-MTA, a para-substituted, non-neurotoxic amphetamine.
