4F-PHP (4′-fluoro-α-pyrrolidinohexanophenone)

Is a synthetic cathinone and a novel psychoactive substance (NPS) in the pyrrolidinophenone family. Structurally analogous to α-PHP, it features a para-fluoro substitution on the phenyl ring, which may enhance blood–brain barrier permeability and alter its pharmacological profile. Emerging in clandestine markets as a “legal high,” 4F-PHP has raised concerns among toxicologists and law enforcement due to its potent stimulant effects and limited safety data.

Chemical Identity and Structure

IUPAC Name: 1-(4-fluorophenyl)-2-pyrrolidin-1-ylhexan-1-one
Common Name: 4F-PHP Chemical Class: Synthetic cathinone / pyrrolidinophenone derivative Molecular Formula: C₁₆H₂₂FNO Molecular Weight: 263.35 g/mol CAS Number: Not universally registered; emerging in NPS databases Physical Form: White to off-white crystalline solid or powder The para-fluorine atom on the phenyl ring and the hexanone backbone distinguish 4F-PHP from α-PHP (no fluoro group) and other shorter-chain analogues, potentially modifying lipophilicity and receptor affinity.
Pharmacodynamics and Mechanism of Action

4F-PHP acts primarily as a dopamine–norepinephrine reuptake inhibitor (DNRI), similar to other synthetic cathinones:
Dopamine transporter (DAT) inhibition: leads to increased extracellular dopamine in reward pathways Norepinephrine transporter (NET) inhibition: elevates sympathetic tone, increasing heart rate and blood pressure Users report rapid onset (minutes when vaporized or insufflated) with euphoric and energizing effects, including heightened alertness, sociability, and psychomotor stimulation.
Toxicity and Adverse Effects

Due to its high potency and narrow therapeutic index, 4F-PHP carries significant health risks:
Cardiovascular: hypertension, tachycardia, arrhythmias, chest pain Neurological: tremors, insomnia, anxiety, agitation, seizures in severe cases Psychiatric: paranoia, hallucinations, compulsive redosing (“binge” pattern) Physical: dehydration, hyperthermia, muscle cramps Overdose can precipitate serotonin syndrome–like features when combined with other serotonergic agents, though primarily a stimulant profile.
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