Isotonitazene

Isotonitazene is a benzimidazole derived opioid analgesic drug related to etonitazene,[1][2] which has been sold as a designer drug.[3][4] It has only around half the potency of etonitazene in animal studies,[1][5][6][7][8][9][10] but it is likely less potent in humans as was seen with etonitazene (1000 times as potent as morphine in animal models yet only 60 times as potent in humans).[1]

Isotonitazene
Clinical data
Routes of
administration		oral, nasal spray, e-vape
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC23H30N4O3
Molar mass410.518 g·mol−1
3D model (JSmol)

Isotonitazene (obtained from an online vendor) was fully characterized in November 2019 in a paper where the authors performed a full analytical structure elucidation in addition to determination of the potency at the μ-opioid receptor using a biological functional assay in vitro. While isotonitazene was not compared directly to morphine in this assay, it was found to be around 2.5 times more potent than hydromorphone and slightly more potent than fentanyl.[1][11]

Side effects

Side effects of benzimidazole derived opioids are expected to be similar to those of fentanyl, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Isotonitazene has been detected in multiple fatalities in the U.S. since August 2019, as reported by NPS Discovery, the Center for Forensic Science Research and Education, and NMS Labs.[12][13]

The US Drug Enforcement Administration issued a notice of intent to publish a temporary order to schedule isotonitazene in Schedule I of the Controlled Substances Act,[14] which came into effect on 20 August 2020.[15]

See also

References
  1. Blanckaert, Peter; Cannaert, Annelies; Uytfanghe, Katleen Van; Hulpia, Fabian; Deconinck, Eric; Calenbergh, Serge Van; Stove, Christophe (2019). "Report on a novel emerging class of highly potent benzimidazole NPS opioids: chemical and in vitro functional characterization of isotonitazene". Drug Testing and Analysis. n/a (n/a): 422–430. doi:10.1002/dta.2738. ISSN 1942-7611. PMID 31743619.
  2. Casy, A. F.; Wright, J. (October 1966). "Ionisation constants and partition coefficients of some analgesically active 2-benzylbenzimidazole derivatives and related compounds". Journal of Pharmacy and Pharmacology. 18 (10): 677–683. doi:10.1111/j.2042-7158.1966.tb07782.x. ISSN 2042-7158. PMID 4382076.
  3. Power M. 40 Americans Are Dying Every Month From Taking this New, Legal Opioid. 2020 Mar 13. Vice.com
  4. Zagorski CM, Myslinski JM, Hill LG. Isotonitazene as a contaminant of concern in the illegal opioid supply: A practical synthesis and cost perspective. Int J Drug Policy. 2020 Sep 22;86:102939. doi:10.1016/j.drugpo.2020.102939 PMID 32977186
  5. Hunger A, Kebrle J, Rossi A, Hoffmann K (October 1957). "[Synthesis of analgesically active benzimidazole derivatives with basic substitutions]" [Synthesis of analgesically active benzimidazole derivatives with basic substitutions]. Experientia. 13 (10): 400–1. doi:10.1007/BF02161116. PMID 13473817. S2CID 32179439.
  6. Rossi A, Hunger A, Kebrle J, Hoffmann K (1960). "Benzimidazol-Derivate und verwandte Heterocyclen. IV. Die Kondensation von o-Phenylendiamin mit α-Aryl- und γ-Aryl-acetessigester" [Benzimidazole derivatives and related heterocycles IV. The condensation of o-phenylenediamine with α-aryl and γ-aryl-acetoacetate]. Helvetica Chimica Acta (in German). 43 (4): 1046–1056. doi:10.1002/hlca.19600430413.
  7. Rossi A, Hunger A, Kebrle J, Hoffmann K (1960). "Benzimidazol-Derivate und verwandte Heterocyclen V. Die Kondensation von o-Phenylendiamin mit aliphatischen und alicyclischen β-Ketoestern" [Benzimidazole derivatives and related heterocycles V. The condensation of o-phenylenediamine with aliphatic and alicyclic β-keto esters]. Helvetica Chimica Acta (in German). 43 (5): 1298–1313. doi:10.1002/hlca.19600430515.
  8. Rossi A, Hunger A, Kebrle J, Hoffmann K (1960). "Benzimidazol-Derivate und verwandte Heterocyclen VI. Synthese von Phenyl-[1-aminoalkyl-benzimidazolyl-(2)]-essigsäure-estern und -amiden" [Benzimidazole derivatives and related Heterocycles VI. Synthesis of phenyl-[1-aminoalkyl-benzimidazolyl-(2)]-acetic acid esters and amides]. Helvetica Chimica Acta (in German). 43 (6): 1727–1733. doi:10.1002/hlca.19600430634.
  9. Rossi A, Hunger A, Kebrle J, Hoffmann K (1961). "Benzimidazol-Derivate und verwandte Heterocyclen VII. Synthese neuer 2-Amino-benzimidazole" [Benzimidazole Derivatives and related Heterocycles VII. Synthesis of new 2-amino-benzimidazole]. Helvetica Chimica Acta (in German). 44 (5): 1273–1282. doi:10.1002/hlca.19610440513.
  10. Gross F, Turrian H (October 1957). "Über Benzimidazolderivate mit starker analgetischer Wirkung" [Benzimidazole derivatives with strong analgesic effects]. Experientia. 13 (10): 401–3. doi:10.1007/BF02161117. PMID 13473818. S2CID 6824038.
  11. Vandeputte, Marthe M.; Cannaert, Annelies; Stove, Christophe P. (July 2020). "In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances". Archives of Toxicology. doi:10.1007/s00204-020-02855-7. ISSN 1432-0738. PMID 32734307. S2CID 220881657.
  12. Krotulski, Alex J.; Papsun, Donna M.; Kacinko, Sherri L.; Logan, Barry K. (February 2020). "Isotonitazene Quantitation and Metabolite Discovery in Authentic Forensic Casework". Journal of Analytical Toxicology. 44 (6): 521–530. doi:10.1093/jat/bkaa016. PMID 32091095.
  13. Shover CL, Falasinnu TO, Freedman RB, Humphreys K. Emerging Characteristics of Isotonitazene-Involved Overdose Deaths: A Case-Control Study. J Addict Med. 2020 Nov 23. doi:10.1097/ADM.0000000000000775 PMID 33234804
  14. "Schedules of Controlled Substances: Temporary Placement of Isotonitazene in Schedule I". Federal Register. 18 June 2020.
  15. "Schedules of Controlled Substances: Temporary Placement of Isotonitazene in Schedule I". Federal Register. 20 August 2020.


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