title: The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers.
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.
authors.affiliation: Experimental Medicine, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. Bror.Jonzon@astrazeneca.com
authors.forename: Bror
authors.initials: B
authors.lastname: Jonzon
authors.forename: Ingvar
authors.initials: I
authors.lastname: Bjarnason
authors.forename: Chris
authors.initials: C
authors.lastname: Hawkey
authors.forename: John
authors.initials: J
authors.lastname: Jones
authors.forename: Andrew
authors.initials: A
authors.lastname: Goddard
authors.forename: Urban
authors.initials: U
authors.lastname: Fagerholm
authors.forename: Pär
authors.initials: P
authors.lastname: Karlsson