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The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers

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Abstract

COX-inhibiting nitric oxide donators (CINODs) are a new class of drugs in development for the treatment of acute and chronic pain. They comprise a COX-inhibiting moiety linked to a nitric-oxide-donating component and are designed to provide an innovative mechanism of action of balanced COX inhibition and controlled nitric oxide donation. Through these pathways, CINODs should provide analgesic and anti-inflammatory efficacy, while offering gastrointestinal safety through the tissue-protective effects of nitric oxide donation. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is the first agent in the CINOD class to enter extensive clinical development. Pre-clinical studies demonstrate that AZD3582 has a superior gastrointestinal safety profile to naproxen, while demonstrating analgesic and anti-inflammatory efficacy. In healthy human volunteers, AZD3582 caused little gastrointestinal damage compared with equimolar doses of naproxen. Studies to evaluate the longer-term gastrointestinal safety of AZD3582, alongside its efficacy in alleviating chronic and acute pain, are ongoing.

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Authors and Affiliations

  1. Experimental Medicine, AstraZeneca R&D Södertälje, S-151 85, Södertälje, Sweden

    Bror Jonzon, Urban Fagerholm & Pär Karlsson

  2. Department of Medicine, Guy's, King's and St. Thomas' School of Medicine, London, UK

    Ingvar Bjarnason

  3. Division of Gastroenterology, Queens Medical Centre, University Hospital, Nottingham, UK

    Chris Hawkey, John Jones & Andrew Goddard

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  1. Bror Jonzon
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Jonzon, B., Bjarnason, I., Hawkey, C. et al. The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers. Inflammopharmacology 11, 437–444 (2003). https://doi.org/10.1163/156856003322699618

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