4-Fluoromethylphenidate (4F-Mph)
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Product Description
4-Fluoromethylphenidate (4F-MPH), also known as 4-FMPH or 4-Fmph, is a synthetic stimulant and a fluorinated analog of methylphenidate (MPH), a prescription medication used to treat attention deficit hyperactivity disorder (ADHD). Unlike MPH, 4F-MPH is not approved for medical use and is primarily encountered as a novel psychoactive substance (NPS) sold online as a "research chemical" or nootropic. It belongs to the phenidate class of compounds and is part of the substituted phenethylamine family. 4F-MPH produces euphoriant, stimulating, and long-lasting effects, often described as more potent than MPH. However, it carries significant risks, including addiction potential, cardiovascular strain, and overdose. Studies have shown that the (±)-threo isomer of 4F-MPH is more potent than MPH in blocking dopamine and norepinephrine uptake, suggesting it may have stronger psychostimulant properties. Cases of fatal and non-fatal intoxication involving 4F-MPH have been reported, highlighting its potential dangers.
Note: The 4-Fluoromethylphenidate (4F-MPH) chemical raw materials produced by our company are only for scientific research and cannot be used for medical purposes.
Synthesis and Production
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Synthesis Method: 4F-MPH is synthesized as a structural analog of methylphenidate (Ritalin®), involving modifications to introduce a fluorine atom at the para position of the phenyl ring. The synthesis typically follows routes similar to those used for methylphenidate and its analogs.
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Production Form: It is typically encountered as a white to off-white powder, often in the form of a hydrochloride salt. The melting point for the hydrochloride salt is around 222°C.
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Commercial Production: It is produced and sold by unregulated online vendors as a "research chemical." Commercial samples are often a mixture of the pharmacologically active (±)-threo diastereomer and the less active (±)-erythro diastereomer, with the threo isomer usually predominating in active products. Its primary commercial classification is as a "pharmaceutical intermediate" or "organic intermediate."
Uses and Application
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Primary Use (Unregulated): Self-Medication for ADHD. Survey and interview data from the provided research paper indicate that 4F-MPH is one of the most commonly used Novel Psychoactive Substances (NPS) for self-medicating symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) and Attention Deficit Disorder (ADD). Users report employing it as a stopgap between conventional treatments, to supplement an existing prescription perceived as insufficient, or due to poor access to formal healthcare (e.g., long wait times, high costs, geographical barriers).
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Recreational Use: It is used recreationally for its stimulant effects, including enhanced focus, euphoria, increased energy, and motivation. User reports often describe it as a "cleaner" or more potent alternative to methylphenidate.
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Research Context: Initially studied in the 1990s as a potential cocaine antagonist. Currently, it exists primarily as a "research chemical" with no approved medical use. It is used in forensic and pharmacological research to understand the effects and risks of novel psychoactive substances.
Properties and Characteristics
A. Chemical & Physical Properties
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IUPAC Name: Methyl (2R)-2-(4-fluorophenyl)-2-[(2R)-piperidin-2-yl]acetate
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Common Name: 4-Fluoromethylphenidate (4F-MPH, 4-FMPH)
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Molecular Formula: C₁₄H₁₈FNO₂
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Molar Mass: 251.30 g/mol
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CAS Numbers: 1253910-15-4, 1354631-33-6, 1354631-26-1
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Chemical Class: Piperidine derivative; halogenated methylphenidate analogue.
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SMILES: COC(=O)C@@HC2=CC=C(C=C2)F
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Structure: Features a piperidine ring attached to a phenyl ring with a fluorine atom at the para position, connected via a carbon bearing a methyl ester group.
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Diastereomers: Exists as threo and erythro diastereomers. The (±)-threo form is responsible for most pharmacological effects, while the (±)-erythro form is significantly less active.
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Appearance: White to off-white powder (typically hydrochloride salt).
B. Pharmacological Properties
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Mechanism of Action: Primarily a Dopamine and Norepinephrine Reuptake Inhibitor (DNRI). It blocks the dopamine transporter (DAT) and norepinephrine transporter (NET), increasing extracellular levels of these neurotransmitters.
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Potency & Selectivity: Data from rat brain synaptosomes shows it is more potent than methylphenidate (MPH):
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Dopamine (DAT): IC₅₀ = 61 nM (vs. MPH IC₅₀ = 131 nM) - ~2x more potent.
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Norepinephrine (NET): IC₅₀ = 31 nM (vs. MPH IC₅₀ = 83 nM) - ~2.7x more potent.
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Serotonin (SERT): IC₅₀ = 8,805 nM - Minimal activity, making it catecholamine-selective.
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Subjectively Reported Effects:
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Desired: Enhanced focus, euphoria, increased energy, motivation, alertness, talkativeness.
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Adverse: Anxiety, paranoia, tachycardia, hypertension, insomnia, vasoconstriction, decreased appetite, jaw clenching.
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Duration of Effects: Reported to be 4–8 hours, potentially longer than methylphenidate.
Safety and Handling
A. Hazards and Adverse Effects
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Neuropsychiatric: Anxiety, panic attacks, paranoia, irritability, and potential to trigger or exacerbate psychosis.
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Cardiovascular: Significant risk of tachycardia (increased heart rate), hypertension (high blood pressure), arrhythmias, and general cardiovascular stress, which can lead to heart attack or stroke.
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Other Acute Effects: Insomnia, severe vasoconstriction, headaches, dizziness, and hyperthermia.
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Chronic Risks: High potential for tolerance, psychological dependence, and addiction. Withdrawal symptoms upon cessation are similar to those of other stimulants.
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Unknown Long-Term Toxicity: The long-term effects and toxicity profile of 4F-MPH and its metabolites are unknown. The fluorination may lead to unique and potentially harmful metabolites.
B. Overdose and Toxicity
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Documented Cases:
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Non-Fatal Intoxication: A case report describes a 26-year-old female who sniffed 4F-MPH and experienced neuropsychiatric and cardiological symptoms for a week, requiring sedation with diazepam. Blood concentration of (±)-threo-4F-MPH was 32 ng/mL.
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Fatal Intoxication: A death in Florida (USA) was attributed to 4F-MPH, marking the first confirmed fatal case. The substance was detected in postmortem blood (concentrations varying from 0.012 to 0.05 mg/L) alongside other substances like 3-methoxy-PCP and methamphetamine.
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C. Harm Reduction Advice
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Dosing: Due to its high potency and lack of quality control, start with a very low dose (e.g., 1-5 mg) to assess individual tolerance.
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Avoid Mixing: Do not combine with other stimulants (including caffeine), alcohol, or depressants, due to the risk of dangerous interactions.
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Frequency: Avoid frequent or daily use to prevent rapid tolerance and dependence.
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Medical Conditions: Contraindicated for individuals with pre-existing cardiovascular or psychiatric conditions.
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Purity: Be aware that products may be mislabeled, impure, or contain other, more potent NPS, as evidenced by drug checking services finding unexpected substances sold as 4F-MPH.
D. Legal Status and Handling
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Legal Status: 4F-MPH is a controlled or illegal substance in many jurisdictions due to its NPS status.
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UK: Class B drug.
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USA: Not explicitly scheduled federally but likely falls under the Federal Analogue Act as an analog of Schedule II methylphenidate. Explicitly banned in some states (e.g., Alabama).
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Canada, Germany, Italy, Turkey: Controlled.
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Handling in Research: In a legitimate research context, handling requires proper chemical hygiene controls, personal protective equipment (PPE), and the use of analytical-grade standards.