4-Fluoroamphetamine (4-FA; 4-FMP; PAL-303; "Flux"), also known as ''para''-fluoroamphetamine (PFA) is a

psychoactive A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

research chemical Research chemicals are chemical substances used by scientists for medical and scientific research purposes. One characteristic of a research chemical is that it is for laboratory research use only; a research chemical is not intended for human o ...

of the

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amin ...

and

substituted amphetamine Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...

chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classificat ...

es. It produces

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

and entactogenic effects. As a

recreational drug Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...

, 4-FA is sometimes sold along with related compounds such as

2-fluoroamphetamine 2-Fluoroamphetamine (2-FA) is a stimulant drug from the amphetamine family which has been sold as a designer drug. 2-Fluoroamphetamine differs from 3- and 4-fluoroamphetamine in the position of the fluorine atom on the aromatic ring, making t ...

and 4-fluoromethamphetamine.

Usage

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-FA has become illegal since May 2017.

Effects

The subjective effects of 4-fluoroamphetamine include

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

which some find similar to the effects of

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...

and amphetamine, increased energy (stimulation), mood elevation, feelings of warmth and empathy, excessive talking,

bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; reports of prevalence range from 8% to 31% in the gene ...

, 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. The dopamine reuptake inhibition produced by 4-FA is stronger than that of either 4-CA or 4-IA. 4-FA also produces less

hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...

than similar compounds such as PMA, 3-MTA and

4-methylamphetamine 4-Methylamphetamine (4-MA; PAL-313; Aptrol; p-TAP) is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes. In vitro, it acts as a potent and balanced serotonin, norepinephrine, and dopamine releasing agent with ...

. Common acute side effects are nausea, headaches, increased heart rate and insomnia.

Chemistry

4-FA reacts with

reagent testing Reagent testing is one of the processes used to identify substances contained within a pill, usually illicit substances. With the increased prevalence of drugs being available in their pure forms, the terms "drug checking" or "pill testing" may a ...

to give a semi-unique array of colors which can be used to aid its identification.

Pharmacology

4-Fluoroamphetamine is a

releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the synapse, release of a monoamine neurotransmitter from the synapse, presynaptic neuron into the synapse, leading to an increase in the extracellular conc ...

and

reuptake inhibitor Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmit ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

, and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

. 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. 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 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

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. 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. It is unclear where

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 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 hi ...

, a ''para''-substituted, non-neurotoxic amphetamine.

Toxicology

The LD₅₀ (mouse; i.p.) of 4-FA is 46 mg/kg. 4-FA was associated with three deaths in Melbourne in 2017 from pills that additionally contained

25C-NBOMe 25C-NBOMe (NBOMe-2C-C, 2C-C-NBOMe, Cimbi-82) is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent ...

Legal status

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

References

External links

Erowid: 4-Fluoroamphetamine
{{DEFAULTSORT:Fluoroamphetamine, 4- Substituted amphetamines Entactogens and empathogens Fluoroarenes Designer drugs Serotonin-norepinephrine-dopamine releasing agents