Isotonitazene: The Latest Substance to Be Banned in the European Union

By Keith Williams, Ph.D. – Business Manager, Analytical Standards Europe, Cayman Chemical

On September 2, 2020, the European Commission announced that it was introducing a ban on the sale of isotonitazene.1 A novel analgesic, isotonitazene has been reported in at least five member states, and there have been reported deaths in Canada and the US as well as Europe due to exposure to this substance.

Although the ban is targeted specifically at isotonitazene, there are a number of related benzimidazole opioid substances that display pharmacological activity and are now being collectively called nitazenes.

Prototypical structure of nitazenes
The core structure of the nitazenes allows for various alterations, and some of these are now starting to appear in several forums.

Originally developed in the 1950s by the pharmaceutical company Ciba AG, they were intended to be used as safer alternatives to morphine. This group of drugs is structurally unrelated to morphine but exerts a significant opioid response.2 Two of them (etonitazene and clonitazene) were placed on Schedule I of the United Nations Single Convention on Narcotic Drugs 1961 at the request of the US government, leaving the other variants uncontrolled. No product was ever brought to the market commercially. A toxicology report published in February 2020 describes the confirmation and quantitation of isotonitazene in blood, urine, and vitreous fluid and profiles in vivo metabolite formation in drug users.3 A technical report was published by the EMCDDA in June 2020 summarising the current position in the illicit market.4 

To help laboratories identify these new psychoactive substances (NPS), Cayman has produced a range of reference materials and analytical standards, covering both parent compounds and metabolites, as well as two isotopically labelled products for use as internal standards. We have collated these products on the first of our Cayman NPS Snapshots, a handy one-page guide that summarises the structures of the various nitazene compounds as well as key historical dates, prototypical structure, and known pharmacology. The snapshot is a useful resource for scientists to familiarize themselves with the new emerging nitazene class. As new products are released, we will update it appropriately.

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