Nifoxipam

Product Name: Nifoxipam Synonyms: 3-Hydroxydesmethylflunitrazepam; DP 370; 5-(2-fluorophenyl)-3-hydroxy-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one1

General Description: Nifoxipam is formally described as 5-(2-fluorophenyl)-3-hydroxy-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one.1 It is a synthetic, psychoactive molecule belonging to the benzodiazepine class (specifically the nitrobenzodiazepine subclass).23 Chemically and pharmacologically, it is a known minor active metabolite of the strictly controlled prescription hypnotic flunitrazepam (commonly known by the trade name Rohypnol), differing via the absence of an N-methyl group and the addition of a hydroxyl group at the 3-position of the diazepine ring.23 Nifoxipam emerged on the European illicit market around 2014 as a novel psychoactive substance (NPS) and designer drug.23

In analytical, clinical, and forensic toxicology, nifoxipam is utilized as a fundamental reference standard.235 It is essential for the calibration of analytical instrumentation (such as LC-MS/MS and GC-MS) and the development of screening methodologies to identify and quantify the substance—or to monitor flunitrazepam metabolism—in seized materials, counterfeit pharmaceutical tablets, or biological matrices (e.g., whole blood, plasma, urine).23

Technical Information:

• CAS Number: 74723-10-71
• Molecular Formula: C₁₅H₁₀FN₃O₄45
• Formula Weight: 315.26 g/mol3
• SMILES: O=C1C(O)N=C(C2=CC=CC=C2F)C3=C(C=CC(N+=O)=C3)N1
• InChI Key: UHFIFTRHLBAWGY-UHFFFAOYSA-N2
• Formulation: Typically supplied as a neat white-to-yellow crystalline solid or as a certified reference material solution (e.g., 1 mg/mL or 100 µg/mL in methanol or acetonitrile).23

Biological Action: Like other classical benzodiazepines, nifoxipam acts as a positive allosteric modulator (PAM) at central GABA_A receptors.23 By enhancing the inhibitory signaling of the neurotransmitter gamma-aminobutyric acid (GABA), it elicits sedative, hypnotic, anxiolytic, muscle relaxant, and amnesic effects.23 Pharmacokinetically, because it already possesses a 3-hydroxyl group, nifoxipam readily undergoes direct Phase II metabolism (glucuronidation) in vivo to form nifoxipam-glucuronide, which is a primary target for urinary forensic drug screening.23

Regulatory and Safety Information:

• Intended Use: This product is intended strictly for use as an analytical reference standard for forensic, toxicological, and academic research purposes.23
• Warning: This product carries a significant risk of central nervous system depression, physiological dependence, and potentially fatal overdose, especially when combined with other depressants such as opioids or alcohol.23 It is not for human or veterinary use.24
• Legal Status: The regulatory status of nifoxipam varies globally.23 In the United Kingdom, it is broadly controlled under the Psychoactive Substances Act 2016.23 In Canada, it is a Schedule IV controlled substance.23 In the United States, nifoxipam is not explicitly scheduled at the federal level under the Controlled Substances Act; however, several individual states have proactively classified it as a Schedule I or Schedule IV controlled substance.23 It is also regulated or banned under generic designer benzodiazepine clauses in numerous European nations.23 Procurement may require relevant local or institutional licenses.23 Handling should only occur within professional laboratory environments using appropriate Personal Protective Equipment (PPE) such as safety glasses, chemical-resistant gloves, and a laboratory coat.23