Fluoroketamine
[CAS# 111982-50-4]

Identification

• Classification: Organic raw materials >> Amino compound >> Cycloalkylamines, aromatic monoamines, aromatic polyamines and derivatives and salts
• Name: Fluoroketamine
• Synonyms: 2-(2-fluorophenyl)-2-(methylamino)cyclohexan-1-one
• Molecular Formula: C₁₃H₁₆FNO
• Molecular Weight: 221.27
• CAS Registry Number: 111982-50-4
• SMILES: CNC1(CCCCC1=O)C2=CC=CC=C2F

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 333.6±42.0 ºC 760 mmHg (Calc.)^*
• Flash point: 155.6±27.9 ºC (Calc.)^*
• Index of refraction: 1.534 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

Fluoroketamine refers to a group of arylcyclohexylamine derivatives structurally related to ketamine in which a fluorine atom is introduced onto the aromatic ring. Ketamine itself was first synthesized in the early 1960s as a safer alternative to phencyclidine (PCP) and has since become widely used as an anesthetic and analgesic. During subsequent decades, structural analogs were developed to investigate the influence of different substituents on pharmacological activity, including fluorinated derivatives. These fluoroketamine compounds were studied primarily within medicinal chemistry programs and later identified in forensic contexts as novel psychoactive substances.

Like ketamine, fluoroketamine derivatives act primarily as noncompetitive antagonists at the N-methyl-D-aspartate (NMDA) receptor, producing dissociative anesthetic effects. Additional activity at opioid receptors, monoamine transporters, and other ion channels has been reported for ketamine and related compounds, and fluorination can influence potency, receptor affinity, and metabolic stability. However, none of the fluoroketamine variants have been developed or approved for medical use, and their pharmacological properties are less well documented compared to ketamine.

Fluoroketamine first appeared on the unregulated drug market in the mid-2010s. Analytical detection of positional isomers such as 2-fluorodeschloroketamine (2-FDCK) and 3-fluorodeschloroketamine (3-FDCK) was reported in forensic casework and toxicology laboratories. These compounds differ from ketamine by lacking a chlorine atom at the aryl position and instead bearing a fluorine atom, leading to distinct chemical and metabolic properties while retaining dissociative effects. Forensic identification was facilitated by the development of reference spectra using gas chromatography–mass spectrometry (GC-MS), liquid chromatography–tandem mass spectrometry (LC-MS/MS), and nuclear magnetic resonance (NMR) spectroscopy.

Applications of fluoroketamine are limited to research and forensic science. In laboratory contexts, these compounds have been investigated to understand how halogen substitution on the aryl group influences dissociative anesthetic activity, pharmacokinetics, and metabolism. In forensic toxicology, fluoroketamine derivatives have been detected in biological samples from impaired driving cases, acute intoxications, and fatalities. These findings highlight their potential for misuse and the associated risks of unpredictable potency and toxicity.

Because fluoroketamine analogs are not licensed pharmaceuticals, their appearance on the recreational drug market has raised public health and regulatory concerns. Jurisdictions have responded by classifying them under controlled substance legislation, often within broader scheduling frameworks that include arylcyclohexylamine derivatives. Their legal status continues to evolve as new derivatives are identified.

Fluoroketamine compounds illustrate how minor structural modifications of established anesthetics can generate new substances with significant pharmacological activity and potential for misuse. While they remain useful in chemical and pharmacological research for studying structure–activity relationships, their non-medical availability and use present challenges for toxicologists, clinicians, and regulatory agencies.

References

2023. Comparative Analysis and Structure Identification of Oxidative Metabolites and Hydrogenation Metabolite Enantiomers for 2-Fluorodeschloroketamine. Journal of Analytical Toxicology, 47(3).
DOI: 10.1093/jat/bkad021
URL: https://pubmed.ncbi.nlm.nih.gov/36947399

2023. Characterization of extensive 2-fluorodeschloroketamine metabolism in pooled human liver microsomes, urine and hair from an addicted patient using high-resolution accurate mass spectrometry. Journal of Analytical Toxicology, 47(6).
DOI: 10.1093/jat/bkad030
URL: https://pubmed.ncbi.nlm.nih.gov/37279563

2021. Metabolite elucidation of 2-fluoro-deschloroketamine (2F-DCK) using molecular networking across three complementary in vitro and in vivo models. Drug Testing and Analysis, 14(1).
DOI: 10.1002/dta.3162
URL: https://pubmed.ncbi.nlm.nih.gov/34515415