What is 2-FDCK? A Complete Research Guide
2-FDCK (2-Fluorodeschloroketamine, also known as fluoroketamine) is a fluorinated arylcyclohexylamine compound structurally related to ketamine. It has emerged as one of the most analytically significant dissociative reference standards in forensic toxicology and pharmacological research, particularly for laboratories developing detection methods for novel NMDA receptor antagonists.
Chemical Structure & Identity
2-FDCK belongs to the arylcyclohexylamine class, sharing the core cyclohexanone scaffold with ketamine, deschloroketamine (DCK), and 3-MeO-PCE. The key structural feature is a fluorine atom at the 2-position of the phenyl ring, replacing the chlorine atom found in ketamine. This seemingly minor change significantly alters metabolic stability and pharmacokinetic properties.
Molecular formula: C₁₃H₁₆FNO
Molecular weight: 221.27 g/mol
CAS number: 111982-49-1
IUPAC: 2-(2-fluorophenyl)-2-(methylamino)cyclohexan-1-one
Melting point: ~225°C (HCl salt)
Mechanism of Action — NMDA Receptor Antagonism
Like ketamine, 2-FDCK acts as a non-competitive antagonist at NMDA (N-methyl-D-aspartate) receptors, binding within the ion channel pore to block glutamatergic transmission. NMDA receptors are ionotropic glutamate receptors critical for synaptic plasticity, long-term potentiation, and excitatory neurotransmission.
The fluorine substitution at the 2-position of the phenyl ring affects receptor binding affinity and duration through electronic and steric effects. Compared to ketamine, 2-FDCK exhibits greater metabolic resistance to CYP3A4-mediated N-demethylation, contributing to a longer apparent duration of action in pharmacological studies.
In addition to NMDA antagonism, arylcyclohexylamines including 2-FDCK show activity at σ (sigma) receptors and dopamine transporter (DAT), which contribute to their complex pharmacological profiles and make them important models for multireceptor CNS research.
Research Applications
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Forensic Toxicology: 2-FDCK is one of the most commonly detected dissociative substances in forensic biological samples across European laboratories. High-purity reference standards are essential for LC-MS/MS and GC-MS method development, validation, and casework confirmation.
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NMDA Receptor Pharmacology: As a structurally simplified ketamine analogue, 2-FDCK serves as a research tool for probing NMDA receptor binding kinetics, channel block duration, and the structural determinants of dissociative pharmacology.
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Metabolite Identification: Phase I metabolism of 2-FDCK involves ring hydroxylation, N-demethylation, and dehydration. Characterising and synthesising metabolite standards is an active area of forensic research requiring highly pure parent compound as starting material.
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Drug Detection Method Development: Wastewater analysis, hair testing, urine immunoassay development, and workplace drug testing all require validated methods with characterised reference standards for 2-FDCK.
Analytical Properties
2-FDCK is commercially available as the hydrochloride salt — a white to off-white crystalline solid with moderate water solubility. Key analytical parameters:
- • UV absorption: ~269 nm (phenyl ring chromophore)
- • GC-MS characteristic ions: m/z 203, 182, 144, 56 (base peak)
- • LC-MS/MS MRM transitions well-characterised in forensic literature
- • Two stereocentres; typically supplied as racemate
- • Stable under acidic conditions; avoid prolonged exposure to strong base
2-FDCK vs Ketamine: Key Differences
| Property | 2-FDCK | Ketamine |
|---|---|---|
| Ring halogen | Fluorine (2-position) | Chlorine (2-position) |
| Molecular weight | 221.27 g/mol | 237.73 g/mol |
| CYP3A4 metabolism | More resistant | Readily N-demethylated |
| Primary use | Research reference standard | Clinical anaesthetic / research |
| Forensic prevalence | High (EU, 2020–2026) | Lower (mostly clinical) |