Etonitazene
[CAS# 911-65-9]

Identification

• Classification: Biochemical >> Inhibitor >> G protein coupled receptor(GPCR & G Protein)
• Name: Etonitazene
• Synonyms: 2-[2-[(4-ethoxyphenyl)methyl]-5-nitrobenzimidazol-1-yl]-N,N-diethylethanamine
• Molecular Formula: C₂₂H₂₈N₄O₃
• Molecular Weight: 396.48
• CAS Registry Number: 911-65-9
• EC Number: 213-009-1
• SMILES: CCN(CC)CCN1C2=C(C=C(C=C2)[N+](=O)[O-])N=C1CC3=CC=C(C=C3)OCC

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 580.7±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 305.0±28.7 ºC (Calc.)^*
• Index of refraction: 1.591 (Calc.)^*

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

Safety Data

• Controlled Substance: DEA Drug Code Number: 9624

Discovory and Applicatios

Etonitazene is a synthetic opioid belonging to the 2-benzylbenzimidazole class of compounds. It was originally synthesized in the mid-20th century as part of efforts to develop potent analgesics that could serve as alternatives to morphine. Chemically, etonitazene features a benzimidazole core substituted with a nitro group and a 2-(diethylamino)ethyl side chain, which together confer high affinity for the μ-opioid receptor. The compound is classified as an extremely potent opioid, with analgesic activity estimated to be several thousand times stronger than morphine on a weight basis.

The pharmacological activity of etonitazene is mediated by its interaction with opioid receptors in the central nervous system. Activation of μ-opioid receptors leads to inhibition of neurotransmitter release, modulation of pain signaling pathways, and the production of analgesia. Due to its high potency, even microgram-level doses can produce significant effects. In addition to analgesia, etonitazene can induce sedation, respiratory depression, and euphoria, similar to other opioids. Its high receptor affinity and lipophilicity allow rapid penetration of the blood-brain barrier, which contributes to both its efficacy and its risk of overdose.

Etonitazene was originally developed as a research compound to explore structure-activity relationships within the benzimidazole opioid family. Its synthesis involves the formation of the benzimidazole ring followed by substitution with appropriate nitro and amine functional groups. These synthetic pathways were studied extensively to understand how modifications of the core structure and side chains influence potency, receptor selectivity, and metabolic stability. The nitro group in particular is known to enhance the potency of benzimidazole opioids by affecting receptor binding and electronic properties of the molecule.

Due to its extremely high potency and the associated risk of respiratory depression and death, etonitazene has not been approved for clinical use. It is classified as a controlled substance in many countries and is primarily encountered in scientific research or in illicit markets. Its pharmacological profile has made it a substance of interest in forensic toxicology, where detection in biological samples requires highly sensitive analytical techniques such as liquid chromatography-mass spectrometry (LC-MS) due to the low concentrations at which it is active.

The metabolism of etonitazene involves both oxidative and reductive pathways. Hepatic enzymes, particularly cytochrome P450 isoforms, mediate N-dealkylation, reduction of the nitro group, and other biotransformations that lead to metabolites with varying degrees of activity. The pharmacokinetics of etonitazene are characterized by rapid absorption, high central nervous system penetration, and potent effects at very low doses. This pharmacological profile underlines the extreme care required in handling and research use.

Etonitazene’s extreme potency also makes it a subject of concern in the context of opioid overdose and public health. Even small quantities can be lethal, and it has occasionally been identified as a contaminant or adulterant in street drugs, contributing to unintentional overdoses. Its detection, quantification, and regulation are therefore critical for forensic and clinical toxicology. Laboratory studies continue to provide information about its receptor interactions, metabolism, and potential analogues, but human use is strictly limited and highly controlled due to safety risks.

Overall, etonitazene represents a class of ultra-potent synthetic opioids with significant analgesic effects mediated through μ-opioid receptor activation. Its chemical structure, including the benzimidazole core, nitro substituent, and diethylaminoethyl side chain, contributes to its high receptor affinity and rapid central nervous system activity. While valuable for research into opioid pharmacology and receptor mechanisms, etonitazene’s extreme potency and toxicity preclude clinical use and demand careful handling under strict regulatory control.

References

2025. The emergence of nitazenes: a new chapter in the synthetic opioid crisis. Archives of Toxicology.
DOI: 10.1007/s00204-025-04102-3

2025. Comprehensive method to detect nitazene analogues and xylazine in wastewater. Environmental Science and Pollution Research.
DOI: 10.1007/s11356-025-36425-0