title: COX-inhibiting nitric oxide donators (CINODs) - a new paradigm in the treatment of pain and inflammation.
abstract: The clinical utility of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief is tempered by their propensity to cause gastrointestinal toxicity. Cyclooxygenase (COX)-inhibiting nitric oxide donators (CINODs) are a new class of drugs designed to provide analgesic efficacy through COX inhibition and gastrointestinal safety through the protective effects of controlled nitric oxide donation. Pre-clinical studies assessing the pharmacology, efficacy and gastrointestinal safety of AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] support this concept. Based on these studies, AZD3582 was the first CINOD to enter clinical development for the treatment of acute and chronic pain. The potential clinical utility of this new class is illustrated by a study of AZD3582 in healthy volunteers in which it caused significantly less acute gastrointestinal toxicity than an equimolar dose of naproxen. The results of the animal studies and the initial clinical study warrant long-term tolerability studies of AZD3582 along with evaluation of its anti-inflammatory and analgesic effects in humans.
authors.affiliation: Research DMPK, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. Janet.Hoogstraate@astrazeneca.com
authors.forename: Janet
authors.initials: J
authors.lastname: Hoogstraate
authors.forename: Lars I
authors.initials: LI
authors.lastname: Andersson
authors.forename: Odd-Geir
authors.initials: OG
authors.lastname: Berge
authors.forename: Bror
authors.initials: B
authors.lastname: Jonzon
authors.forename: Göran
authors.initials: G
authors.lastname: Ojteg