COX-inhibiting NO Donators
To reduce GI and CV side effects, a new class of compounds named COX-inhibiting NO donators have been developed but they are still not commercially available. These compounds are derivative of NSAIDs to incorporate a NO-releasing moiety. NO has important biologic effects on the CV system, including vasodilatory and platelet-inhibitory actions through activation of soluble guanylyl cyclase and consequent formation of cyclic guanosine monophosphate. Moreover, NO is able to protect the gastric mucosa by a number of mechanisms, including promotion of mucous secretion, increased mucosal blood flow, and decreased adherence of neutrophils to the gastric vascular endothelium.
Naproxcinod [(S)-2-(6-Methoxy-2-naphthyl)propanoic acid 4-nitrooxybutyl ester], that is, NO-naproxen, is the first of the class of cyclooxygenase-inhibiting NO donators, and is currently in Phase III clinical development for the treatment of OA. After absorption, it is cleaved to produce naproxen and an NO-donating moiety. Moreover, it has been demonstrated recently that it did not induce elevations of blood pressure) seen with naproxen, and it had similar effects on blood pressure to that of placebo in patients with OA.
Expert Rev Clin Pharmacol. 2011;4(5):605-621. © 2011 Expert Reviews Ltd.
Cite this: Managing the Adverse Effects of Nonsteroidal Anti-inflammatory Drugs - Medscape - Sep 01, 2011.